10,984 results match your criteria demethylation mammals


[Roles of ten eleven translocation proteins family and 5-hydroxymethylcytosine in epigenetic regulation of stem cells and regenerative medicine].

Authors:
J F Zhao D Li Y An

Beijing Da Xue Xue Bao Yi Xue Ban 2021 Feb;53(2):420-424

Department of Plastic Surgery, Peking University Third Hospital, Beijing 100191, China.

The methylation of cytosine is one of the most fundamental epigenetic modifications in mammalian genomes, and is involved in multiple crucial processes including gene expression, cell differentiation, embryo development and oncogenesis. In the past, DNA methylation was thought to be an irreversible process, which could only be diluted passively through DNA replication. It is now becoming increa-singly obvious that DNA demethylation can be an active process and plays a crucial role in biological processes. Read More

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February 2021

B1a and B2 cells are characterized by distinct CpG modification states at DNMT3A-maintained enhancers.

Nat Commun 2021 04 13;12(1):2208. Epub 2021 Apr 13.

Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.

The B1 and B2 lineages of B cells contribute to protection from pathogens in distinct ways. The role of the DNA CpG methylome in specifying these two B-cell fates is still unclear. Here we profile the CpG modifications and transcriptomes of peritoneal B1a and follicular B2 cells, as well as their respective proB cell precursors in the fetal liver and adult bone marrow from wild-type and CD19-Cre Dnmt3a floxed mice lacking DNMT3A in the B lineage. Read More

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Epigenetic regulations in mammalian spermatogenesis: RNA-mA modification and beyond.

Cell Mol Life Sci 2021 Apr 9. Epub 2021 Apr 9.

Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Emerging evidence shows that mA, one of the most abundant RNA modifications in mammals, is involved in the entire process of spermatogenesis, including mitosis, meiosis, and spermiogenesis. "Writers" catalyze mA formation on stage-specific transcripts during male germline development, while "erasers" remove mA modification to maintain a balance between methylation and demethylation. The different functions of RNA-mA transcripts depend on their recognition by "readers". Read More

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[Effect of DR4 Demethylation to the Proliferation and Apoptosis of Myeloid Leukemia K562 Cells].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):422-427

Xinxiang Medical College, Xinxiang 453003, Henan Province, China.

Objective: To investigate the effect of tumor necrosis factor death receptor (DR) 4 demethylation to the proliferation and apoptosis of myeloid leukemia K562 cells.

Methods: The logarithmic phase of K562 cells were treated by desitabine (DCA) at 0, 0.8, 1. Read More

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Glyphosate and AMPA Induce Alterations in Expression of Genes Involved in Chromatin Architecture in Human Peripheral Blood Mononuclear Cells (In Vitro).

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

We have determined the effect of glyphosate and aminomethylphosphonic acid (AMPA) on expression of genes involved in chromatin architecture in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate and AMPA in the concentrations ranging from 0.5 to 100 μM and from 0. Read More

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Anti-Cancer Effects and Tumor Marker Role of Glutathione -Transferase Mu 5 in Human Bladder Cancer.

Int J Mol Sci 2021 Mar 17;22(6). Epub 2021 Mar 17.

Department of Microbiology, Immunology and Biopharmaceuticals, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan.

Our previous study demonstrated that the glutathione -transferase Mu 5 (GSTM5) gene is highly CpG-methylated in bladder cancer cells and that demethylation by 5-aza-dC activates GSTM5 gene expression. The aim of the present study was to investigate the role of GSTM5 in bladder cancer. The levels of GSTM5 gene expression and DNA methylation were analyzed in patients with bladder cancer, and functional studies of GSTM5 were conducted using GSTM5 overexpression in cultured bladder cancer cells. Read More

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FTO-mediated cytoplasmic mA demethylation adjusts stem-like properties in colorectal cancer cell.

Nat Commun 2021 03 19;12(1):1716. Epub 2021 Mar 19.

IGF, Univ. Montpellier, CNRS, INSERM, Montpellier, France.

Cancer stem cells (CSCs) are a small but critical cell population for cancer biology since they display inherent resistance to standard therapies and give rise to metastases. Despite accruing evidence establishing a link between deregulation of epitranscriptome-related players and tumorigenic process, the role of messenger RNA (mRNA) modifications in the regulation of CSC properties remains poorly understood. Here, we show that the cytoplasmic pool of fat mass and obesity-associated protein (FTO) impedes CSC abilities in colorectal cancer through its N,2'-O-dimethyladenosine (mA) demethylase activity. Read More

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Reversible chromatin condensation by the DNA repair and demethylation factor thymine DNA glycosylase.

Nucleic Acids Res 2021 03;49(5):2450-2459

Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.

Chromatin structures (and modulators thereof) play a central role in genome organization and function. Herein, we report that thymine DNA glycosylase (TDG), an essential enzyme involved in DNA repair and demethylation, has the capacity to alter chromatin structure directly through its physical interactions with DNA. Using chemically defined nucleosome arrays, we demonstrate that TDG induces decompaction of individual chromatin fibers upon binding and promotes self-association of nucleosome arrays into higher-order oligomeric structures (i. Read More

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Biotransformation of lincomycin and fluoroquinolone antibiotics by the ammonia oxidizers AOA, AOB and comammox: A comparison of removal, pathways, and mechanisms.

Water Res 2021 May 3;196:117003. Epub 2021 Mar 3.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, China; Sino-Danish Center for Science and Education, University of Chinese Academy of Sciences, Beijing, China.

In this study, we evaluated the biotransformation mechanisms of lincomycin (LIN) and three fluoroquinolone antibiotics (FQs), ciprofloxacin (CFX), norfloxacin (NFX), and ofloxacin (OFX), which regularly enter aquatic environments through human activities, by different ammonia-oxidizing microorganisms (AOM). The organisms included a pure culture of the complete ammonia oxidizer (comammox) Nitrospira inopinata, an ammonia oxidizing archaeon (AOA) Nitrososphaera gargensis, and an ammonia-oxidizing bacterium (AOB) Nitrosomonas nitrosa Nm90. The removal of these antibiotics by the pure microbial cultures and the protein-normalized biotransformation rate constants indicated that LIN was significantly co-metabolically biotransformed by AOA and comammox, but not by AOB. Read More

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The epigenetic pioneer EGR2 initiates DNA demethylation in differentiating monocytes at both stable and transient binding sites.

Nat Commun 2021 03 10;12(1):1556. Epub 2021 Mar 10.

Department of Internal Medicine III, University Hospital Regensburg, 93053, Regensburg, Germany.

The differentiation of human blood monocytes (MO), the post-mitotic precursors of macrophages (MAC) and dendritic cells (moDC), is accompanied by the active turnover of DNA methylation, but the extent, consequences and mechanisms of DNA methylation changes remain unclear. Here, we profile and compare epigenetic landscapes during IL-4/GM-CSF-driven MO differentiation across the genome and detect several thousand regions that are actively demethylated during culture, both with or without accompanying changes in chromatin accessibility or transcription factor (TF) binding. We further identify TF that are globally associated with DNA demethylation processes. Read More

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Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics during early mammalian development.

Nat Commun 2021 02 24;12(1):1286. Epub 2021 Feb 24.

Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Utrecht, The Netherlands.

DNA methylation (5mC) is central to cellular identity. The global erasure of 5mC from the parental genomes during preimplantation mammalian development is critical to reset the methylome of gametes to the cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to 5mC erasure remains unclear. Read More

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February 2021

DNA hypomethylating agents increase activation and cytolytic activity of CD8 T cells.

Mol Cell 2021 04 19;81(7):1469-1483.e8. Epub 2021 Feb 19.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada. Electronic address:

We demonstrate that DNA hypomethylating agent (HMA) treatment can directly modulate the anti-tumor response and effector function of CD8 T cells. In vivo HMA treatment promotes CD8 T cell tumor infiltration and suppresses tumor growth via CD8 T cell-dependent activity. Ex vivo, HMAs enhance primary human CD8 T cell activation markers, effector cytokine production, and anti-tumor cytolytic activity. Read More

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Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation.

Nat Commun 2021 02 16;12(1):1072. Epub 2021 Feb 16.

Univ Paris Est Creteil, Glycobiology, Cell Growth and Tissue Repair Research Unit (Gly-CRRET), Brain and Lung Epigenetics (BLUE), Creteil, France.

In addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Read More

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February 2021

Epigenetic upregulation of ssc-miR-124a following treatment with Clostridium perfringens beta2-toxin attenuates both apoptosis and inflammation in intestinal porcine epithelial cells.

Arch Biochem Biophys 2021 04 12;701:108806. Epub 2021 Feb 12.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, 730070, China; Gansu Research Center for Swine Production Engineering and Technology, Lanzhou, 730070, China. Electronic address:

Clostridium perfringens (C. perfringens) is a globally recognized zoonotic pathogen. It has been reported that the beta2-toxin produced by C. Read More

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Evidence for divergence of DNA methylation maintenance and a conserved inhibitory mechanism from DNA demethylation in chickens and mammals.

Genes Genomics 2021 Mar 8;43(3):269-280. Epub 2021 Feb 8.

Chromosome Engineering Research Center, Tottori University, Yonago, 683-8503, Japan.

Background: DNA methylation is a significant epigenetic modification that is evolutionarily conserved in various species and often serves as a repressive mark for transcription. DNA methylation levels and patterns are regulated by a balance of opposing enzyme functions, DNA methyltransferases, DNMT1/3A/3B and methylcytosine dioxygenases, TET1/2/3. In mice, the TET enzyme converts DNA cytosine methylation (5mC) to 5-hydroxymethylcytosine (5hmC) at the beginning of fertilisation and gastrulation and initiates a global loss of 5mC, while the 5mC level is increased on the onset of cell differentiation during early embryonic development. Read More

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[Effect of semaphorin-3A on the cellular stability of CD4CD25 regulatory T cells induced by lipopolysaccharide].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2020 Dec;32(12):1454-1460

Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.

Objective: To investigate the effect and mechanism of semaphorin-3A (Sema3A) in maintaining the cellular stability of CD4CD25 regulatory T cells (Tregs) induced by lipopolysaccharide (LPS).

Methods: In vitro, using immunomagnetic beads, splenic CD4CD25 Tregs of C57BL/6J mice were isolated and cultured. According to the random number table, the isolated cells were divided into control group (treated with anti-CD3e and anti-CD28 for polyclonal activation), LPS group (on the basis of control group, treated with LPS at the dose of 100 μg/L), LPS + nuclear factor kappa B (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) group (treated with LPS at the dose of 100 μg/L and PDTC at the dose of 25 mg/L), LPS + phosphate buffer solution (PBS) group (treated with LPS at the dose of 100 μg/L and PBS at the volume of 10 μL), LPS + PDTC + recombinant Sema3A (rSema3A) group (treated with LPS at the dose of 100 μg/L, PDTC at the dose of 25 mg/L and rSema3A at the dose of 300 μg/L), and LPS + PBS + rSema3A group (treated with LPS at the dose of 100 μg/L, PBS at the volume of 10 μL and rSema3A at the dose of 300 μg/L). Read More

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December 2020

[The expression and significance of TET gene and 5hmC in chronic rhinosinusitis].

Authors:
Chong Yao Yu Xu

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 01;35(1):52-56

Department of Otolaryngology Head and Neck Surgery,Renmin Hospital of Wuhan University,Wuhan,430061,China.

To investigate the expression and clinical significance of TET gene and 5hmC in chronic sinusitis. Acquiring 20 cases of nasal polyps from chronic sinusitis with polyps(CW), 20 cases of uncinate process tissues from chronic sinusitis without polyps(CS), 10 cases of middle turbinate tissues from patients with nasal septum deviated as normal group(N).The expression of TET gene and 5hmC in chronic sinusitis was measured by immunofluorescence, Western-Blot and Quantitative real-time PCR. Read More

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January 2021

LncRNA Meg3-mediated regulation of the Smad pathway in atRA-induced cleft palate.

Toxicol Lett 2021 May 22;341:51-58. Epub 2021 Jan 22.

Center for Clinical Single-Cell Biomedicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China; School of Public Health, Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Palatal mesenchymal cell proliferation is essential to the process of palatogenesis, and the proliferation of mouse embryonic palate mesenchymal (MEPM) cells is impacted by both all-trans retinoic acid (atRA) and the TGF-β/Smad signaling pathway. The long non-coding RNA (lncRNA) MEG3 has been shown to activate TGF-β/Smad signaling and to thereby regulate cell proliferation, differentiation, and related processes. Herein, we found that atRA treatment (100 mg/kg) promoted Meg3 upregulation in MEPM cells, and that such upregulation was linked to the suppression of MEPM cell proliferation in the context of secondary palate fusion on gestational day (GD) 13 and 14. Read More

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Demethylation of Methylmercury in Bird, Fish, and Earthworm.

Environ Sci Technol 2021 02 21;55(3):1527-1534. Epub 2021 Jan 21.

U.S. Geological Survey, Water Resources Mission Area, Boulder 80303, Colorado, United States.

Toxicity of methylmercury (MeHg) to wildlife and humans results from its binding to cysteine residues of proteins, forming MeHg-cysteinate (MeHgCys) complexes that hinder biological functions. MeHgCys complexes can be detoxified , yet how this occurs is unknown. We report that MeHgCys complexes are transformed into selenocysteinate [Hg(Sec)] complexes in multiple animals from two phyla (a waterbird, freshwater fish, and earthworms) sampled in different geographical areas and contaminated by different Hg sources. Read More

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February 2021

Cell culture NAIL-MS allows insight into human tRNA and rRNA modification dynamics in vivo.

Nat Commun 2021 01 15;12(1):389. Epub 2021 Jan 15.

Department of Chemistry, Ludwig-Maximilians-University Munich, Butenandtstr. 5-13, 81377, Munich, Germany.

Recently, studies about RNA modification dynamics in human RNAs are among the most controversially discussed. As a main reason, we identified the unavailability of a technique which allows the investigation of the temporal processing of RNA transcripts. Here, we present nucleic acid isotope labeling coupled mass spectrometry (NAIL-MS) for efficient, monoisotopic stable isotope labeling in both RNA and DNA in standard cell culture. Read More

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January 2021

Molecular Aspects of Senescence and Organismal Ageing-DNA Damage Response, Telomeres, Inflammation and Chromatin.

Int J Mol Sci 2021 Jan 8;22(2). Epub 2021 Jan 8.

Laboratory of Medical Genetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland.

Cells can become senescent in response to stress. Senescence is a process characterised by a stable proliferative arrest. Sometimes it can be beneficial-for example, it can suppress tumour development or take part in tissue repair. Read More

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January 2021

Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box.

Nat Commun 2021 01 11;12(1):269. Epub 2021 Jan 11.

Wits Research Institute for Malaria, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, and Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, 2193, South Africa.

Chemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel de novo screening of the Medicines for Malaria Venture (MMV) Pandemic Response Box against Plasmodium asexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. Unique chemotypes were identified with both multistage activity or stage-specific activity, including structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity, such as the JmjC inhibitor ML324 and the antitubercular clinical candidate SQ109. Read More

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January 2021

Label-Free and Template-Free Chemiluminescent Biosensor for Sensitive Detection of 5-Hydroxymethylcytosine in Genomic DNA.

Anal Chem 2021 02 11;93(4):1939-1943. Epub 2021 Jan 11.

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, Jinan, Shandong 250014, China.

5-Hydroxymethylcytosine (5hmC) is a modified base present at low levels in various mammalian cells, and it plays essential roles in gene expression, DNA demethylation, and genomic reprogramming. Herein, we develop a label-free and template-free chemiluminescent biosensor for sensitive detection of 5hmC in genomic DNAs based on 5hmC-specific glucosylation, periodate (IO) oxidation, biotinylation, and terminal deoxynucleotidyl transferase (TdT)-assisted isothermal amplification strategy, which we term hmC-GLIB-IAS. This hmC-GLIB-IAS exhibits distinct advantages of bisulfite-free, improved sensitivity, and genome-wide analysis of 5hmC at constant reaction temperature without the involvement of either specially labeled nucleic acid probes or specific templates for signal amplification. Read More

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February 2021

Relative DNA Methylation and Demethylation Efficiencies during Postnatal Liver Development Regulate Hepatitis B Virus Biosynthesis.

J Virol 2021 02 24;95(6). Epub 2021 Feb 24.

Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA

Hepatitis B virus (HBV) transcription and replication increase progressively throughout postnatal liver development with maximal viral biosynthesis occurring at around 4 weeks of age in the HBV transgenic mouse model of chronic infection. Increasing viral biosynthesis is associated with a corresponding progressive loss of DNA methylation. The loss of DNA methylation is associated with increasing levels of 5-hydroxymethylcytosine (5hmC) residues which correlate with increased liver-enriched pioneer transcription factor Forkhead box protein A (FoxA) RNA levels, a rapid decline in postnatal liver DNA methyltransferase (Dnmt) transcripts, and a very modest reduction in ten-eleven translocation (Tet) methylcytosine dioxygenase expression. Read More

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February 2021

Biotransformation of papaverine and in silico docking studies of the metabolites on human phosphodiesterase 10a.

Phytochemistry 2021 Mar 25;183:112598. Epub 2020 Dec 25.

National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, MS, 38677, USA; Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, MS, 38677, USA. Electronic address:

The metabolism of papaverine, the opium benzylisoquinoline alkaloid, with Aspergillus niger NRRL 322, Beauveria bassiana NRRL 22864, Cunninghamella echinulate ATCC 18968 and Cunninghamella echinulate ATCC 1382 has resulted in O-demethylation, O-methylglucosylation and N-oxidation products. Two new metabolites (4″-O-methyl-β-D-glucopyranosyl) 4'-demethyl papaverine and (4″-O-methyl-β-D-glucopyranosyl) 6-demethyl papaverine, (Metabolites 5 and 6) together with 4'-O-demethylated papaverine (Metabolite 1), 3'-O-demethylated papaverine (Metabolite 2), 6-O-demethylated papaverine (Metabolite 3) and papaverine N-oxide (Metabolite 4) were isolated. The structure elucidation of the metabolites was based primarily on 1D, 2D-NMR analyses and HRMS. Read More

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The Enzymatic Decarboxylation Mechanism of 5-Carboxy Uracil: A Comprehensive Quantum Chemical Study.

J Chem Theory Comput 2021 Jan 24;17(1):96-104. Epub 2020 Dec 24.

Chair of Theoretical Chemistry, Department of Chemistry, University of Munich (LMU), D-81377 Munich, Germany.

Dynamic regulation of DNA methylation is an important process for the control of gene expression in mammals. It is believed that in the demethylation pathway of 5-methyl cytosine, the intermediate 5-carboxy cytosine () can be actively decarboxylated alongside the substitution in the base excision repair. For the active decarboxylation of , a decarboxylase has not been identified so far. Read More

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January 2021

Rapamycin ameliorates corneal injury after alkali burn through methylation modification in mouse TSC1 and mTOR genes.

Exp Eye Res 2021 02 23;203:108399. Epub 2020 Dec 23.

School of Life Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address:

Alkali burn to the cornea is one of the most intractable injuries to the eye due to the opacity resulting from neovascularization (NV) and fibrosis. Numerous studies have focused on studying the effect of drugs on alkali-induced corneal injury in mouse, but fewer on the involvement of alkali-induced DNA methylation and the PI3K/AKT/mTOR signaling pathway in the mechanism of alkali-induced corneal injury. Thus, the aim of this study was to determine the involvement of DNA methyltransferase 3 B-madiated DNA methylation and PI3K/AKT/mTOR signaling modulation in the mechanism of alkali-induced corneal injury in a mouse model. Read More

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February 2021

Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency.

Mol Cell 2021 02 21;81(4):859-869.e8. Epub 2020 Dec 21.

Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Penn Epigenetics Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

Active DNA demethylation via ten-eleven translocation (TET) family enzymes is essential for epigenetic reprogramming in cell state transitions. TET enzymes catalyze up to three successive oxidations of 5-methylcytosine (5mC), generating 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), or 5-carboxycytosine (5caC). Although these bases are known to contribute to distinct demethylation pathways, the lack of tools to uncouple these sequential oxidative events has constrained our mechanistic understanding of the role of TETs in chromatin reprogramming. Read More

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February 2021

Cadmium causes hepatopathy by changing the status of DNA methylation in the metabolic pathway.

Toxicol Lett 2021 Apr 15;340:101-113. Epub 2020 Dec 15.

The First School of Clinical Medical, Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China; Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province, Lanzhou, 730000, Gansu, People's Republic of China; Hepatopancreatobiliary Surgery Institute of Gansu Province, Medical College Cancer Center of Lanzhou University, Lanzhou, 730000, Gansu, People's Republic of China. Electronic address:

Toxicity caused by the heavy metal Cadmium leads to liver diseases; this finding has generated interest among researchers. We detected DNA methylation using Whole Genome Bisulfite Sequencing (WGBS) to study the relationship between Cadmium exposure and liver damage. Forty-eight Sprague-Dawley rats were randomly divided into six groups, and given normal saline or 2. Read More

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A Surge of DNA Damage Links Transcriptional Reprogramming and Hematopoietic Deficit in Fanconi Anemia.

Mol Cell 2020 12;80(6):1013-1024.e6

Department of Experimental Radiation Oncology, the University of Texas, MD Anderson Cancer, Houston, TX 77030, USA; Life Sciences Institute, Zhejiang University, Hangzhou 310058, China. Electronic address:

Impaired DNA crosslink repair leads to Fanconi anemia (FA), characterized by a unique manifestation of bone marrow failure and pancytopenia among diseases caused by DNA damage response defects. As a germline disorder, why the hematopoietic hierarchy is specifically affected is not fully understood. We find that reprogramming transcription during hematopoietic differentiation results in an overload of genotoxic stress, which causes aborted differentiation and depletion of FA mutant progenitor cells. Read More

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December 2020