31,336 results match your criteria methylation states

Epigenetic Aging and Hematopoietic Cell Transplantation in Patients With Severe Aplastic Anemia.

Transplant Cell Ther 2021 Apr 16;27(4):313.e1-313.e8. Epub 2021 Jan 16.

Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Cellular aging in hematopoietic cell transplantation (HCT) is important in the context of immune reconstitution and age-related complications. Recently, several DNA-methylation (DNAm)-based biomarkers of aging known as "epigenetic clocks" have been introduced as novel tools to predict cellular age. Here, we used Cox proportional hazards models to assess the possible associations of donor pre-HCT DNAm age, and its post-HCT changes, using the recently published lifespan-associated epigenetic clock known as "DNAm-GrimAge," with outcomes among patients with severe aplastic anemia (SAA). Read More

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DNA methylation and gene expression integration in cardiovascular disease.

Clin Epigenetics 2021 Apr 9;13(1):75. Epub 2021 Apr 9.

Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Dr Aiguader 88, 08003, Barcelona, Spain.

Background: The integration of different layers of omics information is an opportunity to tackle the complexity of cardiovascular diseases (CVD) and to identify new predictive biomarkers and potential therapeutic targets. Our aim was to integrate DNA methylation and gene expression data in an effort to identify biomarkers related to cardiovascular disease risk in a community-based population. We accessed data from the Framingham Offspring Study, a cohort study with data on DNA methylation (Infinium HumanMethylation450 BeadChip; Illumina) and gene expression (Human Exon 1. Read More

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Delineating Racial and Socioeconomic-Related Health Disparities in End-Stage Heart Failure: Insight from Cardiac DNA Methylation.

Am J Physiol Heart Circ Physiol 2021 Apr 9. Epub 2021 Apr 9.

Neurovascular Physiology Laboratory, School of Kinesiology, Auburn University, Auburn, AL 36849, United States.

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Comparative Transcriptome Profiling of mRNA and lncRNA of Ovaries in High and Low Egg Production Performance in Domestic Pigeons ().

Front Genet 2021 23;12:571325. Epub 2021 Mar 23.

Animal Science College, Zhejiang University, Hangzhou, Zhejiang, China.

Egg production performance is one of the most important economic traits in pigeon industry. However, little is known regarding how egg production performance is regulated by long non-coding RNAs (lncRNAs) in pigeons. To evaluate the lncRNAs and mRNAs in ovaries associated with egg production performance in domestic pigeons, high-throughput RNA sequencing of ovaries between high and low egg production performance groups were performed and analyzed in this study. Read More

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Hypothesis and Theory: Roles of Arginine Methylation in C9orf72-Mediated ALS and FTD.

Front Cell Neurosci 2021 23;15:633668. Epub 2021 Mar 23.

ALS Therapy Development Institute, Cambridge, MA, United States.

Hexanucleotide repeat expansion (G4C2) mutations in the gene C9ORF72 account for approximately 30% of familial cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), as well as approximately 7% of sporadic cases of ALS. G4C2 mutations are known to result in the production of five species of dipeptide repeat proteins (DRPs) through non-canonical translation processes. Arginine-enriched dipeptide repeat proteins, glycine-arginine (polyGR), and proline-arginine (polyPR) have been demonstrated to be cytotoxic and deleterious in multiple experimental systems. Read More

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Telomere length and epigenetic age acceleration in adolescents with anxiety disorders.

Sci Rep 2021 Apr 8;11(1):7716. Epub 2021 Apr 8.

Anxiety Disorders Outpatient Program for Children and Adolescents, Protaia, Federal University of Rio Grande do Sul, UFRGS/Hospital de Clínicas de Porto Alegre, HCPA, Porto Alegre, Brazil.

Evidence on the relationship between genetics and mental health are flourishing. However, few studies are evaluating early biomarkers that might link genes, environment, and psychopathology. We aimed to study telomere length (TL) and epigenetic age acceleration (AA) in a cohort of adolescents with and without anxiety disorders (N = 234). Read More

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Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double mutant AML.

Blood 2021 Apr 8. Epub 2021 Apr 8.

Erasmus University Medical Center, Rotterdam, Netherlands.

Transcriptional deregulation is a central event in the development of acute myeloid leukemia (AML). To identify potential disturbances in gene regulation, we conducted an unbiased screen of allele-specific expression (ASE) in 209 AML cases. The gene encoding GATA binding protein 2 (GATA2) displayed ASE more often than any other myeloid or cancer-related gene. Read More

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Caught in Action: X-ray Structure of Thymidylate Synthase with Noncovalent Intermediate Analog.

Biochemistry 2021 Apr 8. Epub 2021 Apr 8.

Department of Chemistry, The University of Iowa, Iowa City, Iowa 52242, United States.

Methylation of 2-deoxyuridine-5'-monophosphate (dUMP) at the C5 position by the obligate dimeric thymidylate synthase (TSase) in the sole biosynthetic pathway to thymidine 5'-monophosphate (dTMP) proceeds by forming a covalent ternary complex with dUMP and cosubstrate 5,10-methylenetetrahydrofolate. The crystal structure of an analog of this intermediate gives important mechanistic insights but does not explain the half-of-the-sites activity of the enzyme. Recent experiments showed that the C5 proton and the catalytic Cys are eliminated in a concerted manner from the covalent ternary complex to produce a noncovalent bisubstrate intermediate. Read More

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Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.

Front Oncol 2021 22;11:620873. Epub 2021 Mar 22.

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States.

Over 21,000 women are diagnosed with ovarian cancer (OC) in the United States each year and over half that number succumb to this disease annually, often due to recurrent disease. A deeper understanding of the molecular events associated with recurrent disease is needed to identify potential targets. Using genome-scale DNA methylation and gene expression data for 16 matched primary-recurrent advanced stage serous epithelial OCs, we discovered that Claudin-1 (1), a tight junction protein, shows a stronger correlation between expression and methylation in recurrent versus primary OC at multiple CpG sites (R= -0. Read More

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Simplified MethylRAD Sequencing to Detect Changes in DNA Methylation at Enhancer Elements in Differentiating Embryonic Stem Cells.

Epigenomes 2020 Dec 1;4(4). Epub 2020 Oct 1.

Department of Biochemistry, Purdue University, West Lafayette, IN 47907, USA.

Differential DNA methylation is characteristic of gene regulatory regions, such as enhancers, which mostly constitute low or intermediate CpG content in their DNA sequence. Consequently, quantification of changes in DNA methylation at these sites is challenging. Given that DNA methylation across most of the mammalian genome is maintained, the use of genome-wide bisulfite sequencing to measure fractional changes in DNA methylation at specific sites is an overexertion which is both expensive and cumbersome. Read More

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December 2020

The structure, function and evolution of a complete human chromosome 8.

Nature 2021 Apr 7. Epub 2021 Apr 7.

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

The complete assembly of each human chromosome is essential for understanding human biology and evolution. Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2. Read More

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Persistent variations of blood DNA methylation associated with treatment exposures and risk for cardiometabolic outcomes in long-term survivors of childhood cancer in the St. Jude Lifetime Cohort.

Genome Med 2021 Apr 6;13(1):53. Epub 2021 Apr 6.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 735, Memphis, TN, 38105, USA.

Background: It is well-established that cancer treatment substantially increases the risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify the DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions. Read More

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Epigenetics in blood-brain barrier disruption.

Fluids Barriers CNS 2021 Apr 6;18(1):17. Epub 2021 Apr 6.

The Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center, 6431 Fannin St. MSB 7.147, Houston, TX, 77030, USA.

The vessels of the central nervous system (CNS) have unique barrier properties. The endothelial cells (ECs) which comprise the CNS vessels contribute to the barrier via strong tight junctions, specific transporters, and limited endocytosis which combine to protect the brain from toxins and maintains brain homeostasis. Blood-brain barrier (BBB) leakage is a serious secondary injury in various CNS disorders like stroke, brain tumors, and neurodegenerative disorders. Read More

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Induced pluripotent stem cell technology: trends in molecular biology, from genetics to epigenetics.

Epigenomics 2021 Apr 7. Epub 2021 Apr 7.

Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

Induced pluripotent stem cell (iPSC) technology, based on autologous cells' reprogramming to the embryonic state, is a new approach in regenerative medicine. Current advances in iPSC technology have opened up new avenues for multiple applications, from basic research to clinical therapy. Thus, conducting iPSC trials have attracted increasing attention and requires an extensive understanding of the molecular basis of iPSCs. Read More

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Attenuation of the Reaction of Michael Acceptors with Biologically Important Nucleophiles.

Bioconjug Chem 2021 Apr 6. Epub 2021 Apr 6.

ProLynx, 455 Mission Bay Boulevard South, Suite 341, San Francisco, California 94158, United States.

β-Elimination of drugs tethered to macromolecular carbamates provides a platform for drug half-life extension. However, the macromolecular Michael acceptor products formed upon drug release can potentially react with biological amines and thiols and may raise concerns about safety. We desired to mitigate this possibility by developing linkers that have predictable rates of β-elimination but suppressed rates of nucleophilic addition to their Michael acceptor products. Read More

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Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age.

J Trop Pediatr 2021 Jan;67(1)

Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley.

Background: Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes-potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang's mortality score (ZMS). Read More

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January 2021

High social status males experience accelerated epigenetic aging in wild baboons.

Elife 2021 Apr 6;10. Epub 2021 Apr 6.

Evolutionary Anthropology, Biology, Duke University, Durham, NC, United States.

Aging, for virtually all life, is inescapable. However, within populations, biological aging rates vary. Understanding sources of variation in this process is central to understanding the biodemography of natural populations. Read More

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"GrimAge," an epigenetic predictor of mortality, is accelerated in major depressive disorder.

Transl Psychiatry 2021 Apr 6;11(1):193. Epub 2021 Apr 6.

Weill Institute for Neurosciences and Department of Psychiatry and Behavioral Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, USA.

Major depressive disorder (MDD) is associated with premature mortality and is an independent risk factor for a broad range of diseases, especially those associated with aging, such as cardiovascular disease, diabetes, and Alzheimer's disease. However, the pathophysiology underlying increased rates of somatic disease in MDD remains unknown. It has been proposed that MDD represents a state of accelerated cellular aging, and several measures of cellular aging have been developed in recent years. Read More

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Methylation quantitative trait locus analysis of chronic postsurgical pain uncovers epigenetic mediators of genetic risk.

Epigenomics 2021 Apr 6. Epub 2021 Apr 6.

Department of Anatomy, Physiology & Cell biology, California National Primate Research Center, University of California, Davis, CA 95616, USA.

Overlap of pathways enriched by single nucleotide polymorphisms and DNA-methylation underlying chronic postsurgical pain (CPSP), prompted pilot study of CPSP-associated methylation quantitative trait loci (meQTL). Children undergoing spine-fusion were recruited prospectively. Logistic-regression for genome- and epigenome-wide CPSP association and DNA-methylation-single nucleotide polymorphism association/mediation analyses to identify meQTLs were followed by functional genomics analyses. Read More

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-Methylation of Self-Immolative Thiocarbamates Provides Insights into the Mechanism of Carbonyl Sulfide Release.

J Org Chem 2021 Apr 5. Epub 2021 Apr 5.

Department of Chemistry and Biochemistry, Materials Science Institute, Knight Campus for Accelerating Scientific Impact, Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403, United States.

Hydrogen sulfide (HS) is an important biomolecule, and self-immolative thiocarbamates have shown great promise as triggerable HS donors with suitable analogous control compounds; however, thiocarbamates with electron-deficient payloads are less efficient HS donors. We report here the synthesis and study of a series of -methylated esterase-triggered thiocarbamates that block the postulated unproductive deprotonation-based pathway for these compounds. The relative reaction profiles for HS release across a series of electron-rich and electron-poor N-Me aniline payloads are examined experimentally and computationally. Read More

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An Esrrb and Nanog Cell Fate Regulatory Module Controlled by Feed Forward Loop Interactions.

Front Cell Dev Biol 2021 19;9:630067. Epub 2021 Mar 19.

Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Cell fate decisions during development are governed by multi-factorial regulatory mechanisms including chromatin remodeling, DNA methylation, binding of transcription factors to specific loci, RNA transcription and protein synthesis. However, the mechanisms by which such regulatory "dimensions" coordinate cell fate decisions are currently poorly understood. Here we quantified the multi-dimensional molecular changes that occur in mouse embryonic stem cells (mESCs) upon depletion of Estrogen related receptor beta (Esrrb), a key pluripotency regulator. Read More

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The histone modification H3K4me3 is altered at the locus in Alzheimer's disease brain.

Future Sci OA 2021 Feb 9;7(4):FSO665. Epub 2021 Feb 9.

University of Exeter Medical School, University of Exeter, Exeter EX2 5DW, UK.

Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n = 59) or low (n = 29) Alzheimer's disease pathology. Read More

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February 2021

Nutrient Exposure Alters Microbial Composition, Structure, and Mercury Methylating Activity in Periphyton in a Contaminated Watershed.

Front Microbiol 2021 19;12:647861. Epub 2021 Mar 19.

Oak Ridge National Laboratory, Environmental Science Division, Oak Ridge, TN, United States.

The conversion of mercury (Hg) to monomethylmercury (MMHg) is a critical area of concern in global Hg cycling. Periphyton biofilms may harbor significant amounts of MMHg but little is known about the Hg-methylating potential of the periphyton microbiome. Therefore, we used high-throughput amplicon sequencing of the 16S rRNA gene, ITS2 region, and Hg methylation gene pair () to characterize the archaea/bacteria, fungi, and Hg-methylating microorganisms in periphyton communities grown in a contaminated watershed in East Tennessee (United States). Read More

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The mA RNA methylation regulates oncogenic signaling pathways driving cell malignant transformation and carcinogenesis.

Mol Cancer 2021 Apr 4;20(1):61. Epub 2021 Apr 4.

Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, 44109, USA.

The mA RNA methylation is the most prevalent internal modification in mammalian mRNAs which plays critical biological roles by regulating vital cellular processes. Dysregulations of the mA modification due to aberrant expression of its regulatory proteins are frequently observed in many pathological conditions, particularly in cancer. Normal cells undergo malignant transformation via activation or modulation of different oncogenic signaling pathways through complex mechanisms. Read More

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Multiomic Predictors of Short-Term Weight Loss and Clinical Outcomes During a Behavioral-Based Weight Loss Intervention.

Obesity (Silver Spring) 2021 Apr 3. Epub 2021 Apr 3.

Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Objective: Identifying predictors of weight loss and clinical outcomes may increase understanding of individual variability in weight loss response. We hypothesized that baseline multiomic features, including DNA methylation (DNAme), metabolomics, and gut microbiome, would be predictive of short-term changes in body weight and other clinical outcomes within a comprehensive weight loss intervention.

Methods: Healthy adults with overweight or obesity (n = 62, age 18-55 years, BMI 27-45 kg/m , 75. Read More

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SLC6A14 and SLC38A5 Drive the Glutaminolysis and Serine-Glycine-One-Carbon Pathways in Cancer.

Pharmaceuticals (Basel) 2021 Mar 4;14(3). Epub 2021 Mar 4.

Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.

The glutaminolysis and serine-glycine-one-carbon pathways represent metabolic reactions that are reprogramed and upregulated in cancer; these pathways are involved in supporting the growth and proliferation of cancer cells. Glutaminolysis participates in the production of lactate, an oncometabolite, and also in anabolic reactions leading to the synthesis of fatty acids and cholesterol. The serine-glycine-one-carbon pathway is involved in the synthesis of purines and pyrimidines and the control of the epigenetic signature (DNA methylation, histone methylation) in cancer cells. Read More

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Between a Rock and a Hard Place: An Epigenetic-Centric View of Testicular Germ Cell Tumors.

Cancers (Basel) 2021 Mar 25;13(7). Epub 2021 Mar 25.

Department of Comparative Biosciences and the Carle Illinois College of Medicine and the Cancer Center of Illinois, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Compared to many common solid tumors, the main genetic drivers of most testicular germ cell tumors (TGCTs) are unknown. Decades of focus on genomic alterations in TGCTs including awareness of a near universal increase in copies of chromosome 12p have failed to uncover exceptional driver genes, especially in genes that can be targeted therapeutically. Thus far, TGCT patients have missed out on the benefits of targeted therapies available to treat most other malignancies. Read More

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The PARP Way to Epigenetic Changes.

Genes (Basel) 2021 Mar 20;12(3). Epub 2021 Mar 20.

Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.

ADP-ribosylation, is a reversible post-translational modification implicated in major biological functions. Poly ADP-ribose polymerases (PARP) are specialized enzymes that catalyze the addition of ADP ribose units from "nicotinamide adenine dinucleotide-donor molecules" to their target substrates. This reaction known as PARylation modulates essential cellular processes including DNA damage response, chromatin remodeling, DNA methylation and gene expression. Read More

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: Genetic Variation, Heritable Methylation and Disease Association.

Int J Mol Sci 2021 Mar 3;22(5). Epub 2021 Mar 3.

Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia.

is a metastable epiallele with accumulating evidence that methylation at this region is heritable, modifiable and associated with disease including risk and progression of cancer. This study investigated the influence of genetic variation and other factors such as age and adult lifestyle on blood DNA methylation in this region. We first sequenced the gene region in multiple-case breast cancer families in which methylation was identified as heritable and associated with breast cancer risk. Read More

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Pan-Cancer Analysis of Human Kinome Gene Expression and Promoter DNA Methylation Identifies Dark Kinase Biomarkers in Multiple Cancers.

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Department of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-5805, USA.

Kinases are a group of intracellular signaling molecules that play critical roles in various biological processes. Even though kinases comprise one of the most well-known therapeutic targets, many have been understudied and therefore warrant further investigation. DNA methylation is one of the key epigenetic regulators that modulate gene expression. Read More

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