Publications by authors named "Jinghua Shi"

31 Publications

Effect of serum vitamin D level before ovarian stimulation on the cumulative live birth rate of women undergoing in vitro fertilization: a retrospective analysis.

Endocr Connect 2022 Jan 1. Epub 2022 Jan 1.

E Ng, Department of Obstetrics and Gynecology, The University of Hong Kong, Hong Kong, Hong Kong.

Objective: Vitamin D receptors are present in the female reproductive tract. Studies on the association between serum vitamin D level and pregnancy rate of in vitro fertilization (IVF) showed inconsistent results and focused on a single fresh or frozen embryo transfer cycle. The objective of our study was to evaluate if serum vitamin D level before ovarian stimulation was associated with the cumulative live birth rate (CLBR) of the first IVF cycle.

Design: Retrospective cohort study.

Methods: Women who underwent the first IVF cycle from 2012 to 2016 at a university-affiliated reproductive medicine center were included. Archived serum samples taken before ovarian stimulation were analyzed for 25(OH)D levels using liquid chromatography-mass spectrometry.

Results: 1,113 had pregnancy outcome from the completed IVF cycle. The median age (25th-75th percentile) of the women was 36 (34-38) years and serum 25(OH)D level was 53.4 (41.9-66.6)nmol/L. The prevalence of vitamin D deficiency (less than 50nmol/L) was 42.2%. The CLBR in the vitamin D deficient group was significantly lower compared to the non-deficient group (43.9%,208/474 vs 50.9%,325/639, p=0.021, unadjusted), and after controlling for women's age, body mass index, antral follicle count, type and duration of infertility. There were no differences in the clinical/ongoing pregnancy rate, live birth rate and miscarriage rate in the fresh cycle between the vitamin D deficient and non-deficient groups.

Conclusions: Vitamin D deficiency was prevalent in infertile women in subtropical Hong Kong. The CLBR of the first IVF cycle in the vitamin D deficient group was significantly lower compared to the non-deficient group.
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http://dx.doi.org/10.1530/EC-21-0444DOI Listing
January 2022

Sequence of the supernumerary B chromosome of maize provides insight into its drive mechanism and evolution.

Proc Natl Acad Sci U S A 2021 06;118(23)

Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO 65211.

B chromosomes are enigmatic elements in thousands of plant and animal genomes that persist in populations despite being nonessential. They circumvent the laws of Mendelian inheritance but the molecular mechanisms underlying this behavior remain unknown. Here we present the sequence, annotation, and analysis of the maize B chromosome providing insight into its drive mechanism. The sequence assembly reveals detailed locations of the elements involved with the and functions of its drive mechanism, consisting of nondisjunction at the second pollen mitosis and preferential fertilization of the egg by the B-containing sperm. We identified 758 protein-coding genes in 125.9 Mb of B chromosome sequence, of which at least 88 are expressed. Our results demonstrate that transposable elements in the B chromosome are shared with the standard A chromosome set but multiple lines of evidence fail to detect a syntenic genic region in the A chromosomes, suggesting a distant origin. The current gene content is a result of continuous transfer from the A chromosomal complement over an extended evolutionary time with subsequent degradation but with selection for maintenance of this nonvital chromosome.
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http://dx.doi.org/10.1073/pnas.2104254118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201846PMC
June 2021

Pregnancy outcomes in women with infertility and coexisting endometriosis and adenomyosis after laparoscopic surgery: a long-term retrospective follow-up study.

BMC Pregnancy Childbirth 2021 May 18;21(1):383. Epub 2021 May 18.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, P. R. China.

Background: Adenomyosis (AM) and endometriosis (EM) often coexist. Laparoscopic surgery is one of the main methods for diagnosing and treating these conditions. This study aims to investigate the pregnancy outcomes of women with infertility with both AM and EM after laparoscopic surgery and to identify the relevant associated factors.

Methods: This is a retrospective study involving women with infertility diagnosed with EM and AM. All patients had undergone laparoscopic surgery and were divided into two groups according to their pregnancy outcomes. Demographic data, operation records, and pregnancy outcomes were collected.

Results: A total of 226 female patients with infertility diagnosed with both AM and EM underwent laparoscopic surgery. Of these, a total of 176 patients completed follow-up. Ninety-seven patients had live births, including 81 full-term and 16 preterm deliveries. The clinical pregnancy and live birth rates were 67.4 and 55.11%, respectively. One hundred thirty-five patients received in vitro fertilization (IVF), with 70 (51.85%) of these patients having live births. Age, endometrioma size, and uterus size were significantly lower in those who had a successful delivery. There was no statistically significant difference in symptoms, except that those who achieved live birth had a lower rate of anaemia (13.40% vs. 25.32%, p = 0.044). The group that did not proceed to have a live birth had a higher percentage of ovarian and peritoneal endometriosis (p < 0.05), while the distribution of deep infiltrating endometriosis and adenomyosis types were similar. Mean uterus diameter (OR: 0.636, 95% CI: 0.434-0.932, p = 0.020) and endometriosis fertility index (EFI) (OR: 1.299, 95% CI: 1.101-1.531, p = 0.002) were significantly correlated with live birth in the multivariable analysis.

Conclusions: Endometriosis and adenomyosis appear to have an adverse effect on pregnancy outcome. These might be related to the size of the uterus and EFI. Obstetricians and gynaecologists should be alert to this potential adverse effect and manage these patients accordingly.
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http://dx.doi.org/10.1186/s12884-021-03851-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132406PMC
May 2021

Silencing of circular RNA ANRIL attenuates oxygen-glucose deprivation and reoxygenation-induced injury in human brain microvascular endothelial cells by sponging miR-622.

Biol Res 2020 Jul 2;53(1):27. Epub 2020 Jul 2.

Department of Critical Care Medicine, Taizhou People's Hospital, Taizhou, Jiangsu, 225300, People's Republic of China.

Background: Circular RNA (circRNA) is highly expressed in the brain tissue, but its molecular mechanism in cerebral ischemia-reperfusion remains unclear. Here, we explored the role and underlying mechanisms of circRNA antisense non-coding RNA in the INK4 locus (circ_ANRIL) in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced cell injury.

Results: The expression of circ_ANRIL in OGD/R-induced human brain microvascular endothelial cells (HBMECs) was significantly up-regulated, while that of miR-622 was significantly down-regulated. Overexpression of circ_ANRIL significantly inhibited the proliferation of OGD/R-induced HBMECs and aggravated OGD/R-induced cell apoptosis. Moreover, circ_ANRIL overexpression further increased the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in OGD/R-treated HBMECs. The results of bioinformatics analysis and luciferase reporter assay indicated that circ_ANRIL served as an miR-622 sponge to negatively regulate the expression of miR-622 in OGD/R-treated HBMECs. Additionally, circ_ANRIL silencing exerted anti-apoptotic and anti-inflammatory effects by positively regulating the expression of miR-622. Furthermore, inhibition of OGD/R-induced activation of the nuclear factor (NF)-κB pathway by circ_ANRIL silencing was significantly reversed by treatment with miR-622 inhibitor.

Conclusions: Knockdown of circ_ANRIL improved OGD/R-induced cell damage, apoptosis, and inflammatory responses by inhibiting the NF-κB pathway through sponging miR-622.
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http://dx.doi.org/10.1186/s40659-020-00295-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7331154PMC
July 2020

Clinical characteristics difference between early and late recurrence of ovarian endometriosis after laparoscopic cystectomy.

Arch Gynecol Obstet 2020 10 24;302(4):905-913. Epub 2020 Jun 24.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Shuaifuyuan No. 1, Dongcheng District, Beijing, 100730, China.

Background: Ovarian endometriosis is the most frequent type of endometriosis. Despite the use of surgery and medication, many patients suffer from recurrence within near future. Currently, there are no effective clinical characteristics available to predict the time to recurrence in ovarian endometriosis patients.

Purpose: To identify the effective clinical indicators for early and late endometrioma recurrence, we compared the clinical characteristics of early and late recurrence after treatment.

Methods: We collected 358 patients with ovarian endometriosis who had a minimum of 5 years of postoperative follow-up after undergoing a laparoscopic excision of ovarian endometrioma performed at Peking Union Medical College Hospital from January 2009 to April 2013.

Results: A total of 358 patients were recruited in the validation set, with a median follow-up time of 83 months (60-120 months). Till the last follow-up, 68 patients exhibited recurrence. Three-year and 5-year recurrence rates were 9.2% and 15.4%, respectively. Univariate analysis in our study showed that patient with endometrioma surgery history had higher incidence of recurrence in 3 years after re-surgery (OR: 5.594, P = 0.029). Univariate and multivariate analyses using the logistic regression showed that the presence of tenesmus before surgery affected the incidence of early recurrence with a ratio of 57.9% (11/19) and 89.5% (17/19) in 3 years and 5 years after surgery, respectively.

Conclusions: Presence of tenesmus before surgery may be linked to the early recurrence of endometrioma.
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http://dx.doi.org/10.1007/s00404-020-05657-5DOI Listing
October 2020

Exosomal MicroRNA-126 from RIPC Serum Is Involved in Hypoxia Tolerance in SH-SY5Y Cells by Downregulating DNMT3B.

Mol Ther Nucleic Acids 2020 Jun 25;20:649-660. Epub 2020 Apr 25.

Beijing Key Laboratory of Hypoxic Conditioning Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, PRC. Electronic address:

Ischemic tolerance in the brain can be induced by transient limb ischemia, and this phenomenon is termed remote ischemic preconditioning (RIPC). It still remains elusive how this transfer of tolerance occurs. Exosomes can cross the blood-brain barrier, and some molecules may transfer neuroprotective signals from the periphery to the brain. Serum miRNA-126 is associated with ischemic stroke, and exosomal miRNA-126 has shown protective effects against acute myocardial infarction. Therefore, this study aims to explore whether exosomal miRNA-126 from RIPC serum can play a similar neuroprotective role. Exosomes were isolated from the venous serum of four healthy young male subjects, both before and after RIPC. Exosomal miRNA-126 was measured by real-time PCR. The miRNA-126 target sequence was predicted by bioinformatics software. SH-SY5Y neuronal cells were incubated with exosomes, and the cell cycle was analyzed by flow cytometry. The expression and activity of DNA methyltransferase (DNMT) 3B, a potential target gene of miRNA-126, were examined in SH-SY5Y cells. The cell viability of SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD) was also investigated. To confirm the association between miRNA-126 and DNMT3B, we overexpressed miRNA-126 in SH-SY5Y cells using lentiviral transfection. miRNA-126 expression was upregulated in RIPC exosomes, and bioinformatics prediction showed that miRNA-126 could bind with DNMT3B. DNMT levels and DNMT3B activity were downregulated in SH-SY5Y cells incubated with RIPC exosomes. After overexpression of miRNA-126 in SH-SY5Y cells, global methylation levels and DNMT3B gene expression were downregulated in these cells, consistent with the bioinformatics predictions. RIPC exosomes can affect the cell cycle and increase OGD tolerance in SH-SY5Y cells. RIPC seems to have neuroprotective effects by downregulating the expression of DNMTs in neural cells through the upregulation of serum exosomal miRNA-126.
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http://dx.doi.org/10.1016/j.omtn.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210387PMC
June 2020

Effects of green waste addition on waste activated sludge and fat, oil and grease co-digestion in mesophilic batch digester.

Environ Technol 2021 Jul 29;42(18):2870-2884. Epub 2020 Jan 29.

Key Laboratory of the Three Gorges Reservoir Region's Eco-environments, Ministry of Education, College of Environment and Ecology, Chongqing University, Chongqing, People's Republic of China.

Anaerobic digestion (AD) is regarded as an effective method to treat waste activated sludge (WAS) and fat, oil and grease (FOG). Co-digestion of WAS/FOG could promote the methane yield but it will cause acid and salinity inhibition. Green waste (GW) was added into the digesters, and its effects on co-digestion of WAS and FOG in the mesophilic batch digester were investigated. Digestive performances (such as hydrolysis, acidogenesis and methanogenesis) were studied emphatically. The results showed that digester L6 (WAS:FOG:GW = 1:2:1, VS basis) presented the highest specific methane yield (SMY, 341.5 mL/g VS). The results of kinetics study verified that there was a slower hydrolysis rate when GW was applied as a co-substrate, which could reduce the potential of acid inhibition. Volatile fatty acid (VFA) and electrical conductivity analysis showed that GW addition could keep moderate VFA concentrations and alleviate the negative effects of high-salinity substrates on the digestive systems. The microbial community and diversity analysis proved that GW addition was beneficial to keep the balance of hydrolytic bacteria, acidogens and acetogens. The results of this study indicated that GW addition could enhance the energy recovery and system stability in the WAS/FOG co-digestive system.
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http://dx.doi.org/10.1080/09593330.2020.1717641DOI Listing
July 2021

Genome-Scale Sequence Disruption Following Biolistic Transformation in Rice and Maize.

Plant Cell 2019 02 16;31(2):368-383. Epub 2019 Jan 16.

Department of Genetics, University of Georgia, Athens, Georgia 30602

Biolistic transformation delivers nucleic acids into plant cells by bombarding the cells with microprojectiles, which are micron-scale, typically gold particles. Despite the wide use of this technique, little is known about its effect on the cell's genome. We biolistically transformed linear 48-kb phage lambda and two different circular plasmids into rice () and maize () and analyzed the results by whole genome sequencing and optical mapping. Although some transgenic events showed simple insertions, others showed extreme genome damage in the form of chromosome truncations, large deletions, partial trisomy, and evidence of chromothripsis and breakage-fusion bridge cycling. Several transgenic events contained megabase-scale arrays of introduced DNA mixed with genomic fragments assembled by nonhomologous or microhomology-mediated joining. Damaged regions of the genome, assayed by the presence of small fragments displaced elsewhere, were often repaired without a trace, presumably by homology-dependent repair (HDR). The results suggest a model whereby successful biolistic transformation relies on a combination of end joining to insert foreign DNA and HDR to repair collateral damage caused by the microprojectiles. The differing levels of genome damage observed among transgenic events may reflect the stage of the cell cycle and the availability of templates for HDR.
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http://dx.doi.org/10.1105/tpc.18.00613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447018PMC
February 2019

Association of metformin use with ovarian cancer incidence and prognosis: a systematic review and meta-analysis.

Int J Gynecol Cancer 2019 01;29(1):140-146

Department of Endocrinology, Taian City Central Hospital, Taian, People's Republic of China

Background: Some clinical and basic research studies have indicated that exposure to metformin might have protective effects against ovarian cancer. However, results from epidemiologic studies have been inconsistent. We performed a meta-analysis to evaluate the effect of metformin use on the risk of ovarian cancer occurrence and mortality.

Methods: Multiple databases were searched to identify studies on the association between use of metformin and risk of ovarian cancer or prognosis, up to August 2018. Relevant information for analysis was extracted. A random-effects model was used to calculate the pooled risk estimate.

Results: Thirteen articles were included, of which six articles focused on ovarian cancer incidence and the others focused on prognosis. The pooled OR for ovarian cancer occurrence and mortality comparing metformin use with non-use or use of other hypoglycemic drugs was 0.76 (95% CI 0.62 to 0.93, p = 0.008) and 0.55 (95% CI 0.36 to 0.84, p = 0.006), respectively. Moderate to substantial heterogeneity was observed across included studies.

Conclusions: Our findings demonstrate that use of metformin was significantly associated with a lower incidence and a better prognosis of ovarian cancer in patients with diabetes. Well-designed interventional studies are warranted to confirm our findings.
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http://dx.doi.org/10.1136/ijgc-2018-000060DOI Listing
January 2019

Persistent megalocystic ovaries after ovarian hyperstimulation syndrome in a postpartum patient with polycystic ovarian syndrome: a case report.

J Ovarian Res 2018 Sep 10;11(1):79. Epub 2018 Sep 10.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital (PUMCH), Peking Union Medical College, Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China.

Background: Ovary enlargement is common in controlled ovarian stimulation, which could continue several months during a successful pregnancy. However, persistent megalocystic ovaries 3 years after ovarian hyperstimulation syndrome (OHSS) were rare. Here we will present you the case and treatment as well as discuss the probable etiology.

Case Presentation: A 34-year-old woman with polycystic ovarian syndrome (PCOS) and a history of infertility presented to the Department of Obstetrics and Gynecology at Peking Union Medical College Hospital with abdominal pain and persistently enlarged ovaries 36 months after OHSS. Enlarged ovaries were evaluated with ultrasonography and serum tests. Diagnostic laparoscopic surgery with detorsion and drainage followed by GnRHa treatment was performed. Symptoms and ovarian size evaluated by vaginal ultrasound were the main outcome measures. The patient was discharged from the hospital 5 days after surgery without any remarkable complications. Both ovaries recovered to almost normal after a monthly injection of GnRHa for 3 months.

Conclusions: Ovarian enlargement may persist for a long time in patients with severe OHSS even after sex hormone levels and ovarian functions return to normal. Long term follow-up is necessary and ovarian torsion should be suspected when accompanied by abdominal pain. Acupuncture plus GnRHa treatment may be an effective way for these cases.
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http://dx.doi.org/10.1186/s13048-018-0451-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130071PMC
September 2018

Mesophilic anaerobic co-digestion of residual sludge with different lignocellulosic wastes in the batch digester.

Bioresour Technol 2018 Nov 27;268:371-381. Epub 2018 Jul 27.

Key Laboratory of the Three Gorges Reservoir Region's Eco-Environments, Ministry of Education, Institute of Urban Construction and Environmental Engineering, Chongqing University, 174 Shapingba Road, Chongqing 400045, PR China.

Co-digestion of residual sludge (RS) and different lignocellulosic wastes (LWs) including greening waste (GW), decocted Chinese herbs waste (DCHW) and sugarcane bagasse waste (SCBW) was investigated in batch digester. Results show that the application of GW presented the highest specific methane yield (161 mL CH/g VS) due to its high carbohydrate fraction and more balanced C/N ratio in co-substrate mixture. Buswell equation was applied and it is found that biodegradability index (BI) for co-digestion varied from 68.1% to 74.2% (53.0% for RS mono-digestion) depending on the lignin fractions of the LWs. Variation of pH, VFAs, alkalinity and ammonia throughout the digestion were also examined. The addition of LWs induced VFAs formation, as well as their conversion to methane. The higher microbial diversity in RS/LWs co-digestion further confirmed the positive effect of LWs addition in co-digestion.
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http://dx.doi.org/10.1016/j.biortech.2018.07.129DOI Listing
November 2018

The maize W22 genome provides a foundation for functional genomics and transposon biology.

Nat Genet 2018 09 30;50(9):1282-1288. Epub 2018 Jul 30.

Horticultural Sciences Department, University of Florida, Gainesville, FL, USA.

The maize W22 inbred has served as a platform for maize genetics since the mid twentieth century. To streamline maize genome analyses, we have sequenced and de novo assembled a W22 reference genome using short-read sequencing technologies. We show that significant structural heterogeneity exists in comparison to the B73 reference genome at multiple scales, from transposon composition and copy number variation to single-nucleotide polymorphisms. The generation of this reference genome enables accurate placement of thousands of Mutator (Mu) and Dissociation (Ds) transposable element insertions for reverse and forward genetics studies. Annotation of the genome has been achieved using RNA-seq analysis, differential nuclease sensitivity profiling and bisulfite sequencing to map open reading frames, open chromatin sites and DNA methylation profiles, respectively. Collectively, the resources developed here integrate W22 as a community reference genome for functional genomics and provide a foundation for the maize pan-genome.
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http://dx.doi.org/10.1038/s41588-018-0158-0DOI Listing
September 2018

A review of the risk factors, genetics and treatment of endometriosis in Chinese women: a comparative update.

Reprod Health 2018 May 21;15(1):82. Epub 2018 May 21.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, 1# Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

Endometriosis is one of the major causes of economic burden and compromised quality of life in a very large percentage of Asian women. While it is perceived as a benign condition, recent research has shown that it may be a significant cause of infertility and metastatic cancer. It has also been associated with other diseases linked to the functioning of the immune system. Genetic as well as environmental factors are known to affect the manifestation and progression of endometriosis. This review aims to summarize recent research pertaining to the risk factors, diagnosis and treatment of endometriosis in Chinese women. It also provides an overview of identified genetic mutations and polymorphisms and their effects on the risk of developing endometriosis in the Chinese population. A comparison has been drawn between Asian and European-American female populations and the differences in risk factors and treatment responses have been summarized. Since traditional Chinese medicine (TCM) is often used to treat endometriosis, wherever possible, a comparison between efficacies of Western medicine and TCM in the Chinese population has also been provided. Although much progress has been made in the treatment and resolution of endometriosis, several gaps remain and this review also highlights possible areas of future research and advancement that can result in an improvement in patient outcomes and quality of life.
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http://dx.doi.org/10.1186/s12978-018-0506-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963030PMC
May 2018

The Relationship of Circular RNAs With Ovarian Endometriosis.

Reprod Sci 2018 08 28;25(8):1292-1300. Epub 2018 Feb 28.

1 Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

Circular RNAs (circRNAs) are involved in the pathogenesis of many diseases, although their expression pattern and role in endometriosis remains unknown. Therefore, here, we profiled the expression patterns of circRNAs in ovarian ectopic and paired eutopic endometria as well as constructed a circRNA-miRNA-mRNA network. Circular RNA and messenger RNA (mRNA) expression profiles were assessed by a microarray analysis in 4 patients. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of 8 circRNAs and mRNAs was conducted in another 37 patients. We detected 1258 up- and 1061 downregulated circRNAs as well as 1900 up- and 2535 downregulated mRNAs between the ectopic and eutopic endometria. Functional analysis suggested that most differentially expressed mRNAs participate in immune-inflammatory responses and cell cycle regulation. The qRT-PCR validation results for 5 circRNAs ( circ_0004712, circ_0002198, circ_0003570, circ_0008951, and circ_0017248) and 8 mRNAs ( SCN3B, ENTPD1, IL16, BACH2, C3, CKS2, G0S2, and PGRMC1) matched the microarray results. On basis of target prediction, we constructed a circRNA-miRNA-mRNA network. This revealed the primary roles of cancer-related, purine metabolism, glycerophospholipid metabolism, and thyroid hormone signaling pathways in endometriosis pathogenesis. This is the first study of circRNA expression patterns in ovarian endometriosis, which suggests that circRNAs are candidate factors in the activation of ovarian endometriosis and are promising diagnostic biomarkers and treatment targets.
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http://dx.doi.org/10.1177/1933719118759439DOI Listing
August 2018

Single-molecule sequencing and optical mapping yields an improved genome of woodland strawberry (Fragaria vesca) with chromosome-scale contiguity.

Gigascience 2018 02;7(2):1-7

Department of Plant Sciences, University of California - Davis, Davis, California, 95616.

Background: Although draft genomes are available for most agronomically important plant species, the majority are incomplete, highly fragmented, and often riddled with assembly and scaffolding errors. These assembly issues hinder advances in tool development for functional genomics and systems biology.

Findings: Here we utilized a robust, cost-effective approach to produce high-quality reference genomes. We report a near-complete genome of diploid woodland strawberry (Fragaria vesca) using single-molecule real-time sequencing from Pacific Biosciences (PacBio). This assembly has a contig N50 length of ∼7.9 million base pairs (Mb), representing a ∼300-fold improvement of the previous version. The vast majority (>99.8%) of the assembly was anchored to 7 pseudomolecules using 2 sets of optical maps from Bionano Genomics. We obtained ∼24.96 Mb of sequence not present in the previous version of the F. vesca genome and produced an improved annotation that includes 1496 new genes. Comparative syntenic analyses uncovered numerous, large-scale scaffolding errors present in each chromosome in the previously published version of the F. vesca genome.

Conclusions: Our results highlight the need to improve existing short-read based reference genomes. Furthermore, we demonstrate how genome quality impacts commonly used analyses for addressing both fundamental and applied biological questions.
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http://dx.doi.org/10.1093/gigascience/gix124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5801600PMC
February 2018

Improved maize reference genome with single-molecule technologies.

Nature 2017 06 12;546(7659):524-527. Epub 2017 Jun 12.

Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.
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http://dx.doi.org/10.1038/nature22971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052699PMC
June 2017

The transotic approach for vestibular schwannoma: indications and results.

Eur Arch Otorhinolaryngol 2017 Aug 6;274(8):3041-3047. Epub 2017 Jun 6.

Department of Otorhinolaryngology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.

To analyze retrospectively the indications and the results obtained with the transotic approach in a series of patients with vestibular schwannoma. The study included 36 patients from 2007 to 2013 with a vestibular schwannoma that was removed with a transotic approach. All patients underwent preoperative pure tone audiometry, evaluation of facial function and CT and MR imaging. All patients having (1) a hearing loss of more than 50 dB, (2) an average tumor size of 2.7 cm (range 0.5-5.0 cm) and (3) signs of a contracted mastoid (high jugular bulb, anteriorly located sigmoid sinus, low middle cranial fossa, or reduced pneumatization) were selected. The tumor was totally removed in 34 and near-totally removed in 2 patients. The facial nerve was preserved in all patients. The postoperative facial function after 6 weeks was House-Brackmann grade I in 7, grade II in 27, and grade III in 2 patients. All patients presented postoperatively with unilateral total deafness. Seven patients experienced transitory postoperative imbalance. There were two patients who required revision surgery, one with intracranial hemorrhage and another with a CSF leak. There were no deaths and no severe complications such as hemiplegia or intracranial infections. The transotic approach has proven to be of value for the removal of vestibular schwannomas up to 5.0 cm in the presence of temporal bone contraction. Hearing was not preserved; however, other clinical outcomes were very favorable, including high rates of total tumor removal and facial nerve preservation, and low rates of complications.
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http://dx.doi.org/10.1007/s00405-017-4627-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5500681PMC
August 2017

Synergistic Effect of the Combination of Novel Suberoylanilide Hydroxamic Acid Derivatives with Cisplatin on Anti-proliferation of Human Cancer Cells.

Med Chem 2016 ;12(8):767-774

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

A novel, green, and atom-economical boric acid catalyzed direct amidation without the use of any coupling agents for the preparation of suberoylanilide hydroxamic acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is provided. The new SAHA-based inhibitor B123, when used alone, exhibited higher anti-proliferative activities than SAHA or Cisplatin against a number of human cancer cells. We have examined the effect of combination of these SAHA-based inhibitors with Cisplatin. We found synergistic effects of the combination of SAHA-based inhibitors with Cisplatin over a wide range of concentrations against human liver cancer cells HepG2 and two human lung cancer cell lines H1299 and H460. This synergism leads up to 8-fold of dose reduction for Cisplatin in the combination with our synthesized inhibitor B123 against H1299.
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http://dx.doi.org/10.2174/1573406412666160404125551DOI Listing
July 2017

[Response of potassium channels to estrogen and progesterone in the uterine smooth muscle cells of adenomyosis in vitro].

Zhonghua Fu Chan Ke Za Zhi 2015 Nov;50(11):843-7

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China.

Objective: To investigate the expression of potassium channels and the influence of estrogen and progesterone on the cultured uterine smooth muscle cells (USMC) of adenomyosis in vitro.

Methods: There were 22 cases of adenomyosis hysterectomy in the adenomyosis group and 12 patients with cervical intraepithelial neoplasia III removal of the uterus in the control group. USMC were separated and cultured in vitro, incubated with different concentrations of estrogen and progesterone. We used reverse transcription-PCR to dectect the expression of large-conductance calcium- and voltage-sensitive potassium channel α subunit (BKCa α) and voltage-gated potassium channel 4.3 (Kv4.3).

Results: The mRNA expression of BKCa α and Kv4.3 in the adenomyosis group (4.43±2.05 and 4.52±1.97) were significantly higher than those in the control group (0.83±0.25 and 0.86±0.19, P<0.05). In the control group, Kv4.3 mRNA decreased after treated with 0.1 nmol/L (0.17±0.10) and 1.0 nmol/L (0.13±0.08) estrogen than before (0.55±0.29, P<0.05). In the adenomyosis group, BKCa α mRNA decreased significantly after treated with 10.0 nmol/L estrogen (0.56±0.27 versus 1.01±0.35, P<0.05). 0.1 µmol/L progesterone elevated both BKCa α mRNA (0.44±0.24 versus 0.16±0.09) and Kv4.3 mRNA (1.29±0.51 versus 0.55±0.29) in the control group (all P<0.05); however, there were no significant difference in adenomyosis group of different concentration of progestrone (P>0.05).

Conclusion: There is an abnormal expression of potassium channels in the adenomyosis USMC, which is regulated by high concentration of estrogen and might be resistant to progesterone.
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November 2015

Synthesis and Anti-tumor Activities of Novel Phenyl Substituted Suberoylanilide Hydroxamic Acid Derivatives Against Human Cancer Cells.

Med Chem 2015 ;11(7):636-48

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

A facile and atom-economical boric acid catalyzed direct amidation without any coupling agents for the preparation of Suberoylanilide Hydroxamic Acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is described. It is applicable to the preparation of SAHA-based inhibitors having an unprotected hydroxyl group in the phenyl ring without the need of the protection. The in-vitro assays data indicate that the nature and the position of the substituents (activating and/or deactivating) in the capping group (phenyl ring) of SAHA-based inhibitors synthesized in this study have a vital impact on the potency of anti-proliferative activity against cancer cells. With low toxicity toward the normal cells, a number of synthesized SAHA-based inhibitors with two substituents in the phenyl ring possess higher antiproliferative activity than SAHA and Cisplatin toward six studied cancer cell lines: A375 human skin cancer cells, A549 human lung cancer cells, MGC80-3 human gastric cancer cells, H460 human lung cancer cells, H1299 human lung cancer cells, and HepG2 human liver cancer cells. Cisplatin is a common chemotherapeutic drug with high cytotoxicity for a variety of cancer treatments. The inhibitors provided in this study might signify future therapeutic drugs for cancer treatment.
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http://dx.doi.org/10.2174/1573406411666150429154107DOI Listing
July 2016

Model-independent evaluation of tumor markers and a logistic-tree approach to diagnostic decision support.

J Healthc Eng 2014 ;5(4):393-409

Department of Industrial Engineering and Logistics Management, Shanghai Jiaotong University, Shanghai, P. R. China.

Sensitivity and specificity of using individual tumor markers hardly meet the clinical requirement. This challenge gave rise to many efforts, e.g., combing multiple tumor markers and employing machine learning algorithms. However, results from different studies are often inconsistent, which are partially attributed to the use of different evaluation criteria. Also, the wide use of model-dependent validation leads to high possibility of data overfitting when complex models are used for diagnosis. We propose two model-independent criteria, namely, area under the curve (AUC) and Relief to evaluate the diagnostic values of individual and multiple tumor markers, respectively. For diagnostic decision support, we propose the use of logistic-tree which combines decision tree and logistic regression. Application on a colorectal cancer dataset shows that the proposed evaluation criteria produce results that are consistent with current knowledge. Furthermore, the simple and highly interpretable logistic-tree has diagnostic performance that is competitive with other complex models.
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http://dx.doi.org/10.1260/2040-2295.5.4.393DOI Listing
March 2015

Diversity and evolution of centromere repeats in the maize genome.

Chromosoma 2015 Mar 5;124(1):57-65. Epub 2014 Sep 5.

Department of Plant Sciences, University of California Davis, Davis, CA, 95616, USA.

Centromere repeats are found in most eukaryotes and play a critical role in kinetochore formation. Though centromere repeats exhibit considerable diversity both within and among species, little is understood about the mechanisms that drive centromere repeat evolution. Here, we use maize as a model to investigate how a complex history involving polyploidy, fractionation, and recent domestication has impacted the diversity of the maize centromeric repeat CentC. We first validate the existence of long tandem arrays of repeats in maize and other taxa in the genus Zea. Although we find considerable sequence diversity among CentC copies genome-wide, genetic similarity among repeats is highest within these arrays, suggesting that tandem duplications are the primary mechanism for the generation of new copies. Nonetheless, clustering analyses identify similar sequences among distant repeats, and simulations suggest that this pattern may be due to homoplasious mutation. Although the two ancestral subgenomes of maize have contributed nearly equal numbers of centromeres, our analysis shows that the majority of all CentC repeats derive from one of the parental genomes, with an even stronger bias when examining the largest assembled contiguous clusters. Finally, by comparing maize with its wild progenitor teosinte, we find that the abundance of CentC likely decreased after domestication, while the pericentromeric repeat Cent4 has drastically increased.
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http://dx.doi.org/10.1007/s00412-014-0483-8DOI Listing
March 2015

Hollow metal-organic framework polyhedra synthesized by a CO2-ionic liquid interfacial templating route.

J Colloid Interface Sci 2014 Feb 15;416:198-204. Epub 2013 Nov 15.

CAS Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

We proposed for the first time a CO2-ionic liquid (IL) interfacial templating route for the production of hollow MOF microparticles. By adding the gaseous CO2 into IL phase under stirring, a large number of CO2 bubbles are generated, which provide numerous CO2-IL interfaces, serving as the nucleation or agglomeration centers for the MOF nanocrystals. By this strategy, the hollow and mesoporous Zn-BTC (BTC: 1,3,5-benzenetricarboxylic) tetrahedroids were fabricated. The morphologies of the Zn-BTC polyhedra can be easily controlled by CO2 pressure. The as-synthesized Zn-BTC hollow microparticles have shown potential applications in gas separation and catalysis. Furthermore, the CO2-IL interface templating approach has been successfully applied to the fabrication of microsized Zn-BDC (BDC: 1,4-benzenedicarboxylic) hollow prisms.
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http://dx.doi.org/10.1016/j.jcis.2013.10.041DOI Listing
February 2014

Cost-effectiveness of adjuvant FOLFOX and 5FU/LV chemotherapy for patients with stage II colon cancer.

Med Decis Making 2013 05 11;33(4):521-32. Epub 2013 Jan 11.

Carbone Comprehensive Cancer Center, University of Wisconsin–Madison, Madison, Wisconsin (SL)

Purpose: We evaluated the cost-effectiveness of adjuvant chemotherapy using 5-fluorouracil, leucovorin (5FU/LV), and oxaliplatin (FOLFOX) compared with 5FU/LV alone and 5FU/LV compared with observation alone for patients who had resected stage II colon cancer.

Methods: We developed 2 Markov models to represent the adjuvant chemotherapy and follow-up periods and a single Markov model to represent the observation group. We used calibration to estimate the transition probabilities among different toxicity levels. The base case considered 60-year-old patients who had undergone an uncomplicated hemicolectomy for stage II colon cancer and were medically fit to receive 6 months of adjuvant chemotherapy. We measured health outcomes in quality-adjusted life-years (QALYs) and estimated costs using 2007 US dollars.

Results: In the base case, adjuvant chemotherapy of the FOLFOX regimen had an incremental cost-effectiveness ratio (ICER) of $54,359/QALY compared with the 5FU/LV regimen, and the 5FU/LV regimen had an ICER of $14,584/QALY compared with the observation group from the third-party payer perspective. The ICER values were most sensitive to 5-year relapse probability, cost of adjuvant chemotherapy, and the discount rate for the FOLFOX arm, whereas the ICER value of 5FU/LV was most sensitive to the 5-year relapse probability, 5-year survival probability, and the relapse cost. The probabilistic sensitivity analysis indicates that the ICER of 5FU/LV is less than $50,000/QALY with a probability of 99.62%, and the ICER of FOLFOX as compared with 5FU/LV is less than $50,000/QALY and $100,000/QALY with a probability of 44.48% and 97.24%, respectively.

Conclusion: Although adjuvant chemotherapy with 5FU/LV is cost-effective at all ages for patients who have undergone an uncomplicated hemicolectomy for stage II colon cancer, FOLFOX is not likely to be cost-effective as compared with 5FU/LV.
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http://dx.doi.org/10.1177/0272989X12470755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3960917PMC
May 2013

Follicle loss after laparoscopic treatment of ovarian endometriotic cysts.

Int J Gynaecol Obstet 2011 Dec 29;115(3):277-81. Epub 2011 Sep 29.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Objective: To evaluate follicle loss and its associated factors during laparoscopic cystectomy for ovarian endometrioma.

Method: Between October 2008 and December 2009, 140 patients with ovarian cysts undergoing laparoscopic cystectomy at Peking Union Medical Hospital were enrolled: 74 had ovarian endometrioma with no preoperative hormonal therapy (group A), 40 had ovarian endometrioma pretreated with GnRHa (group B), and 26 had non-endometriotic cysts (group C). Pre-, peri- , and postoperative clinical data were collected, and cyst specimens were evaluated histologically.

Results: The number of capsules showing follicles and the mean number of follicles per capsule were lower in group C than in group A or B (P<0.05). Fewer type IIC than type IIB endometriomas showed follicles (P<0.05). The number of follicles per cyst was related negatively to disease duration but positively to pain severity. Women in group A with unilateral endometrioma had a lower mean dysmenorrhea score after the surgery (P<0.05), but no change in basal follicle-stimulating hormone (FSH).

Conclusion: The type of cyst, disease duration, and severity of dysmenorrhea were associated with ovarian follicle loss during laparoscopic excision of endometrioma. Laparoscopic unilateral cystectomy for endometrioma was effective in relieving pain but had little effect on serum FSH, which might reflect the remaining ovarian reserve.
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http://dx.doi.org/10.1016/j.ijgo.2011.07.026DOI Listing
December 2011

An intelligent decision support algorithm for diagnosis of colorectal cancer through serum tumor markers.

Comput Methods Programs Biomed 2010 Nov 25;100(2):97-107. Epub 2010 Mar 25.

Department of Industrial Engineering and Logistics Management, Shanghai Jiao Tong University, Dong Chuan Road 800, Minhang District, Shanghai 200240, China.

Nowadays, a wide range of serum tumor markers can be applied in the diagnosis of colorectal cancer. There exists a wide variability in the type and number of routinely used markers so that, sometimes, patients may receive redundant or insufficient checks. Furthermore, the traditional single cutoff point also hinders the efficient utilization of the continuous check value of a tumor marker. In order to improve the diagnostic accuracy (DA) and decrease the cost, it is necessary to optimize the check combinations and exploit the check values fully. To this end, focusing on colorectal cancer (CRC), an artificial intelligent algorithm entitled DS-STM (diagnosis strategy of serum tumor makers) is developed in this paper. DS-STM can provide decision support for physicians on the usage of different tumor markers and diagnosis of colorectal cancer (CRC). The study demonstrates that, instead of five or more tumor markers, two markers are already enough for diagnosis for most CRC patients. The experimental study shows, compared to the traditional serial test, DS-STM can improve DA from 67.53% to 73.87% for the same validation dataset. In addition, a significant cost reduction can be achieved with the new developed diagnosis strategy.
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http://dx.doi.org/10.1016/j.cmpb.2010.03.001DOI Listing
November 2010

Widespread gene conversion in centromere cores.

PLoS Biol 2010 Mar 9;8(3):e1000327. Epub 2010 Mar 9.

Department of Plant Biology, University of Georgia, Athens, Georgia, United States of America.

Centromeres are the most dynamic regions of the genome, yet they are typified by little or no crossing over, making it difficult to explain the origin of this diversity. To address this question, we developed a novel CENH3 ChIP display method that maps kinetochore footprints over transposon-rich areas of centromere cores. A high level of polymorphism made it possible to map a total of 238 within-centromere markers using maize recombinant inbred lines. Over half of the markers were shown to interact directly with kinetochores (CENH3) by chromatin immunoprecipitation. Although classical crossing over is fully suppressed across CENH3 domains, two gene conversion events (i.e., non-crossover marker exchanges) were identified in a mapping population. A population genetic analysis of 53 diverse inbreds suggests that historical gene conversion is widespread in maize centromeres, occurring at a rate >1x10(-5)/marker/generation. We conclude that gene conversion accelerates centromere evolution by facilitating sequence exchange among chromosomes.
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http://dx.doi.org/10.1371/journal.pbio.1000327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834711PMC
March 2010

Maize centromere structure and evolution: sequence analysis of centromeres 2 and 5 reveals dynamic Loci shaped primarily by retrotransposons.

PLoS Genet 2009 Nov 20;5(11):e1000743. Epub 2009 Nov 20.

Molecular Biosciences and Bioengineering, University of Hawaii, Honolulu, Hawaii, USA.

We describe a comprehensive and general approach for mapping centromeres and present a detailed characterization of two maize centromeres. Centromeres are difficult to map and analyze because they consist primarily of repetitive DNA sequences, which in maize are the tandem satellite repeat CentC and interspersed centromeric retrotransposons of maize (CRM). Centromeres are defined epigenetically by the centromeric histone H3 variant, CENH3. Using novel markers derived from centromere repeats, we have mapped all ten centromeres onto the physical and genetic maps of maize. We were able to completely traverse centromeres 2 and 5, confirm physical maps by fluorescence in situ hybridization (FISH), and delineate their functional regions by chromatin immunoprecipitation (ChIP) with anti-CENH3 antibody followed by pyrosequencing. These two centromeres differ substantially in size, apparent CENH3 density, and arrangement of centromeric repeats; and they are larger than the rice centromeres characterized to date. Furthermore, centromere 5 consists of two distinct CENH3 domains that are separated by several megabases. Succession of centromere repeat classes is evidenced by the fact that elements belonging to the recently active recombinant subgroups of CRM1 colonize the present day centromeres, while elements of the ancestral subgroups are also found in the flanking regions. Using abundant CRM and non-CRM retrotransposons that inserted in and near these two centromeres to create a historical record of centromere location, we show that maize centromeres are fluid genomic regions whose borders are heavily influenced by the interplay of retrotransposons and epigenetic marks. Furthermore, we propose that CRMs may be involved in removal of centromeric DNA (specifically CentC), invasion of centromeres by non-CRM retrotransposons, and local repositioning of the CENH3.
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http://dx.doi.org/10.1371/journal.pgen.1000743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776974PMC
November 2009

P311-induced myofibroblasts exhibit ameboid-like migration through RalA activation.

Exp Cell Res 2006 Oct 28;312(17):3432-42. Epub 2006 Jul 28.

Department of Pathology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.

We previously showed that P311, an intracellular protein involved in cell migration, is found in human wound myofibroblast precursors (proto-myofibroblasts) and myofibroblasts. Furthermore, by binding to the TGF-beta1 latency associated protein (LAP), P311 induced NIH 3T3 cells to transform into non-fibrogenic myofibroblasts characterized by lack of TGF-beta1 production. Here we demonstrate that P311-induced myofibroblasts migrate in an ameboid rather than a mesenchymal pattern. Ameboid migration is characterized by lack of focal adhesions and stress fibers, absence of integrins and MMPs clustering/activation and changes in small GTPases activity, all leading to increased cell motility. P311-induced ameboid migration depended on activation of the GTPase RalA and was reverted to mesenchymal-type migration by RalA RNA interference. Ameboid migration was conserved in cells plated on fibrin, the initial wound matrix, but was switched back to mesenchymal-type migration by collagen I, the main ECM component in late stages of wound healing. TGF-beta1, the major stimulus of collagen production during wound repair, also reversed the ameboid phenotype to mesenchymal. Our studies therefore suggest that, by inducing RalA activity, P311 promotes a motile proto-myofibroblast and myofibroblast phenotype specifically adapted to rapidly populate the initial wound matrix.
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http://dx.doi.org/10.1016/j.yexcr.2006.07.016DOI Listing
October 2006

Partitioning of the maize epigenome by the number of methyl groups on histone H3 lysines 9 and 27.

Genetics 2006 Jul 19;173(3):1571-83. Epub 2006 Apr 19.

Department of Pathology, University of Georgia, Athens, Georgia 30602, USA.

We report a detailed analysis of maize chromosome structure with respect to seven histone H3 methylation states (dimethylation at lysine 4 and mono-, di-, and trimethylation at lysines 9 and 27). Three-dimensional light microscopy and the fine cytological resolution of maize pachytene chromosomes made it possible to compare the distribution of individual histone methylation events to each other and to DNA staining intensity. Major conclusions are that (1) H3K27me2 marks classical heterochromatin; (2) H3K4me2 is limited to areas between and around H3K27me2-marked chromomeres, clearly demarcating the euchromatic gene space; (3) H3K9me2 is restricted to the euchromatic gene space; (4) H3K27me3 occurs in a few (roughly seven) focused euchromatic domains; (5) centromeres and CENP-C are closely associated with H3K9me2 and H3K9me3; and (6) histone H4K20 di- and trimethylation are nearly or completely absent in maize. Each methylation state identifies different regions of the epigenome. We discuss the evolutionary lability of histone methylation profiles and draw a distinction between H3K9me2-mediated gene silencing and heterochromatin formation.
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http://dx.doi.org/10.1534/genetics.106.056853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1526679PMC
July 2006
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