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https://www.readbyqxmd.com/read/28648900/tet-catalyzed-5-hydroxymethylation-precedes-hnf4a-promoter-choice-during-differentiation-of-bipotent-liver-progenitors
#1
Pierre-Benoit Ancey, Szilvia Ecsedi, Marie-Pierre Lambert, Fazlur Rahman Talukdar, Marie-Pierre Cros, Denise Glaise, Diana Maria Narvaez, Veronique Chauvet, Zdenko Herceg, Anne Corlu, Hector Hernandez-Vargas
Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1)-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity...
June 19, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28647531/a-rapid-mass-spectrometric-method-for-the-measurement-of-catalytic-activity-of-ten-eleven-translocation-enzymes
#2
Babu Sudhamalla, Debasis Dey, Megan Breski, Kabirul Islam
Enzymatic methylation at carbon five on cytosine (5mC) in DNA is a hallmark of mammalian epigenetic programming and is critical to gene regulation during early embryonic development. It has recently been shown that dynamic erasure of 5mC by three members of the ten-eleven translocation (TET) family plays a key role in cellular differentiation. TET enzymes belong to Fe (II)- and 2-ketoglutarate (2KG) dependent dioxygenases that successively oxidize 5mC to 5-hydroxymethyl cytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxycytosine (5CaC), thus providing a chemical basis for the removal of 5mC which once was thought to be a permanent mark in mammalian genome...
June 21, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28629775/8-oxo-7-8-dihydroguanine-friend-and-foe-epigenetic-like-regulator-versus-initiator-of-mutagenesis
#3
REVIEW
Aaron M Fleming, Cynthia J Burrows
A high flux of reactive oxygen species during oxidative stress results in oxidative modification of cellular components including DNA. Oxidative DNA "damage" to the heterocyclic bases is considered deleterious because polymerases may incorrectly read the modifications causing mutations. A prominent member in this class is the oxidized guanine base 8-oxo-7,8-dihydroguanine (OG) that is moderately mutagenic effecting G→T transversion mutations. Recent reports have identified that formation of OG in G-rich regulatory elements in the promoters of the VEGF, TNFα, and SIRT1 genes can increase transcription via activation of the base excision repair (BER) pathway...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28607180/p53-is-essential-for-dna-methylation-homeostasis-in-na%C3%A3-ve-embryonic-stem-cells-and-its-loss-promotes-clonal-heterogeneity
#4
Ayala Tovy, Adam Spiro, Ryan McCarthy, Zohar Shipony, Yael Aylon, Kendra Alton, Elena Ainbinder, Noa Furth, Amos Tanay, Michelle Barton, Moshe Oren
DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in naïve mouse ESCs (mESCs), p53 restricts the expression of the de novo DNA methyltransferases Dnmt3a and Dnmt3b while up-regulating Tet1 and Tet2, which promote DNA demethylation. The DNA methylation imbalance in p53-deficient (p53(-/-)) mESCs is the result of augmented overall DNA methylation as well as increased methylation landscape heterogeneity...
June 12, 2017: Genes & Development
https://www.readbyqxmd.com/read/28592103/-association-of-etheno-dna-adduct-and-dna-methylation-level-among-workers-exposed-to-diesel-engine-exhaust
#5
M L Shen, Z N He, X Zhang, H W Duan, Y Niu, P Bin, M Ye, T Meng, Y F Dai, S F Yu, W Chen, Y X Zheng
Objective: To investigate the association between etheno-DNA adduct and the promoter of DNA methylation levels of cyclin dependent kinase inhibitor 2A (P16), Ras association domain family 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in workers with occupational exposure to diesel engine exhaust (DEE). Methods: We recruited 124 diesel engine testing workers as DEE exposure group and 112 water pump operator in the same area as control group in Henan province in 2012 using cluster sampling. The demographic data were obtained by questionnaire survey; urine after work and venous blood samples were collected from each subject...
June 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28586322/dna-n-6-methyladenine-in-metazoans-functional-epigenetic-mark-or-bystander
#6
Guan-Zheng Luo, Chuan He
The DNA-adenine modification N(6)-methyladenine (6mA), initially thought to be mainly restricted to prokaryotes and certain unicellular eukaryotes, has recently been found in metazoans. Proposed functions vary from gene activation to transposon suppression. However, since most metazoan genomes possess 5-methylcytosine (5mC) as a dominant epigenetic mark, it raises the question of why 6mA is required. This Perspective summarizes the latest discoveries and suggests potential functional roles for 6mA in metazoan genomes...
June 6, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28584398/tumor-necrosis-factor-%C3%AE-decreases-ec-sod-expression-through-dna-methylation
#7
Shunpei Morisawa, Hiroyuki Yasuda, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
Extracellular-superoxide dismutase (EC-SOD) is a secreted antioxidative enzyme, and its presence in vascular walls may play an important role in protecting the vascular system against oxidative stress. EC-SOD expression in cultured cell lines is regulated by various cytokines including tumor necrosis factor-α (TNF-α). TNF-α is a major mediator of pathophysiological conditions and may induce or suppress the generation of various types of mediators. Epigenetics have been defined as mitotically heritable changes in gene expression that do not affect the DNA sequence, and include DNA methylation and histone modifications...
May 2017: Journal of Clinical Biochemistry and Nutrition
https://www.readbyqxmd.com/read/28555658/tet-mediated-active-dna-demethylation-mechanism-function-and-beyond
#8
REVIEW
Xiaoji Wu, Yi Zhang
In mammals, DNA methylation in the form of 5-methylcytosine (5mC) can be actively reversed to unmodified cytosine (C) through TET dioxygenase-mediated oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), followed by replication-dependent dilution or thymine DNA glycosylase (TDG)-dependent base excision repair. In the past few years, biochemical and structural studies have revealed mechanistic insights into how TET and TDG mediate active DNA demethylation...
May 30, 2017: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/28531315/the-interaction-between-cytosine-methylation-and-processes-of-dna-replication-and-repair-shape-the-mutational-landscape-of-cancer-genomes
#9
Rebecca C Poulos, Jake Olivier, Jason W H Wong
Methylated cytosines (5mCs) are frequently mutated in the genome. However, no studies have yet comprehensively analysed mutation-methylation associations across cancer types. Here we analyse 916 cancer genomes, together with tissue type-specific methylation and replication timing data. We describe a strong mutation-methylation association across colorectal cancer subtypes, most interestingly in samples with microsatellite instability (MSI) or Polymerase epsilon (POLE) exonuclease domain mutations. By analysing genomic regions with differential mismatch repair (MMR) efficiency, we suggest a possible role for MMR in the correction of 5mC deamination events, potentially accounting for the high rate of 5mC mutation accumulation in MSI tumours...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529766/genome-wide-profiling-of-dna-5-hydroxymethylcytosine-during-rat-sertoli-cell-maturation
#10
Miriam Landfors, Jostein Johansen, Jan Magnus Aronsen, Cathrine Broberg Vågbø, Louis C Doré, Chuan He, Ivar Sjaastad, Pål Sætrom, Péter Fedorcsák, John Arne Dahl, Håvard Aanes, Markus Fußer, Arne Klungland
Sertoli cells have dual roles during the cells' lifetime. In the juvenile mammal, Sertoli cells proliferate and create the structure of the testis, and during puberty they cease to proliferate and take on the adult role of supporting germ cells through spermatogenesis. Accordingly, many genes expressed in Sertoli cells during testis formation are repressed during spermatogenesis. 5-Hydroxymethylcytosine (5hmC) is a DNA modification enzymatically generated from 5mC and present in all investigated mammalian tissues at varying levels...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28520399/immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#11
Shangwei Zhong, Zhe Li, Ting Jiang, Xiangjun Li, Hailin Wang
DNA 5-hydroxymethylcytosine (5hmC) is an important epigenetic modification found in various mammalian cells. Immunofluorescence imaging analysis essentially provides visual pictures for the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes, packaged into chromatins, and further bound with many functional proteins. These physiologically relevant events would generate barriers to the anti-5hmC antibody to selectively recognize 5hmC in DNA. By taking advantage of these naturally generated barriers, here, we present a strategy to evaluate the accessibility of DNA 5hmC in chromatins in situ...
June 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28516982/colorimetric-and-electrochemical-quantification-of-global-dna-methylation-using-a-methyl-cytosine-specific-antibody
#12
Md Hakimul Haque, Ripon Bhattacharjee, Md Nazmul Islam, Vinod Gopalan, Nam-Trung Nguyen, Alfred K Lam, Muhammad J A Shiddiky
We report a simple colorimetric (naked-eye) and electrochemical method for the rapid, sensitive and specific quantification of global methylation levels using only 25 ng of input DNA. Our approach utilises a three-step strategy; (i) initial adsorption of the extracted, purified and denatured bisulfite-treated DNA on a screen-printed gold electrode (SPE-Au), (ii) immuno-recognition of methylated DNA using a horseradish peroxidase (HRP)-conjugated methylcytosine (HRP-5mC) antibody and (iii) subsequent colorimetric detection by the enzymatic oxidation of 3,3',5,5'-tetramethylbenzidin (TMB)/H2O2 which generated a blue-coloured product in the presence of methylated DNA and HRP-5mC immunocomplex...
May 18, 2017: Analyst
https://www.readbyqxmd.com/read/28510608/the-biomphalaria-glabrata-dna-methylation-machinery-displays-spatial-tissue-expression-is-differentially-active-in-distinct-snail-populations-and-is-modulated-by-interactions-with-schistosoma-mansoni
#13
Kathrin K Geyer, Umar H Niazi, David Duval, Céline Cosseau, Chad Tomlinson, Iain W Chalmers, Martin T Swain, David J Cutress, Utibe Bickham-Wright, Sabrina E Munshi, Christoph Grunau, Timothy P Yoshino, Karl F Hoffmann
BACKGROUND: The debilitating human disease schistosomiasis is caused by infection with schistosome parasites that maintain a complex lifecycle alternating between definitive (human) and intermediate (snail) hosts. While much is known about how the definitive host responds to schistosome infection, there is comparably less information available describing the snail's response to infection. METHODOLOGY/PRINCIPLE FINDINGS: Here, using information recently revealed by sequencing of the Biomphalaria glabrata intermediate host genome, we provide evidence that the predicted core snail DNA methylation machinery components are associated with both intra-species reproduction processes and inter-species interactions...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28499883/the-role-of-5-hydroxymethylcytosine-in-development-aging-and-age-related-diseases
#14
REVIEW
V López, A F Fernández, M F Fraga
DNA methylation at the fifth position of cytosines (5mC) represents a major epigenetic modification in mammals. The recent discovery of 5-hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our view of the epigenome, as multiple studies indicate that 5hmC is not simply an intermediate of DNA demethylation, but a genuine epigenetic mark that may play an important functional role in gene regulation. Currently, the availability of platforms that discriminates between the presence of 5mC and 5hmC at single-base resolution is starting to shed light on the functions of 5hmC...
May 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#15
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28467834/nickel-ii-inhibits-tet-mediated-5-methylcytosine-oxidation-by-high-affinity-displacement-of-the-cofactor-iron-ii
#16
Ruichuan Yin, Jiezhen Mo, Jiayin Dai, Hailin Wang
Ten-eleven translocation (Tet) family proteins are Fe(II)- and 2-oxoglutarate-dependent dioxygenases that regulate the dynamics of DNA methylation by catalyzing the oxidation of DNA 5-methylcytosine (5mC). To exert physiologically important functions, redox-active iron chelated in the catalytic center of Tet proteins directly involves the oxidation of the multiple substrates. To understand the function and interaction network of Tet dioxygenases, it is interesting to obtain high affinity and a specific inhibitor...
May 8, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#17
Eugene Gladyshev, Nancy Kleckner
Most eukaryotic genomes contain substantial amounts of repetitive DNA organized in the form of constitutive heterochromatin and associated with repressive epigenetic modifications, such as H3K9me3 and C5 cytosine methylation (5mC). In the fungus Neurospora crassa, H3K9me3 and 5mC are catalyzed, respectively, by a conserved SUV39 histone methyltransferase, DIM-5, and a DNMT1-like cytosine methyltransferase, DIM-2. Here we show that DIM-2 can also mediate repeat-induced point mutation (RIP) of repetitive DNA in N...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28433420/dna-methylation-program-in-normal-and-alcohol-induced-thinning-cortex
#18
Nail Can Öztürk, Marisol Resendiz, Hakan Öztürk, Feng C Zhou
While cerebral underdevelopment is a hallmark of fetal alcohol spectrum disorders (FASD), the mechanism(s) guiding the broad cortical neurodevelopmental deficits are not clear. DNA methylation is known to regulate early development and tissue specification through gene regulation. Here, we examined DNA methylation in the onset of alcohol-induced cortical thinning in a mouse model of FASD. C57BL/6 (B6) mice were administered a 4% alcohol (v/v) liquid diet from embryonic (E) days 7-16, and their embryos were harvested at E17, along with isocaloric liquid diet and lab chow controls...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28428825/comprehensive-evaluation-of-genome-wide-5-hydroxymethylcytosine-profiling-approaches-in-human-dna
#19
Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M Gould, Shalima S Nair, Susan J Clark, Clare Stirzaker
BACKGROUND: The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping the mammalian DNA methylation landscape. The gold-standard bisulphite conversion technologies to study DNA methylation do not distinguish between 5mC and 5hmC. However, new approaches to mapping 5hmC genome-wide have advanced rapidly, although it is unclear how the different methods compare in accurately calling 5hmC...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28413450/fetal-testis-organ-culture-reproduces-the-dynamics-of-epigenetic-reprogramming-in-rat-gonocytes
#20
Arlette Rwigemera, Fabien Joao, Geraldine Delbes
BACKGROUND: Epigenetic reprogramming is a critical step in male germ cell development that occurs during perinatal life. It is characterized by the remodeling of different epigenetic marks such as DNA methylation (5mC) and methylation of histone H3. It has been suggested that endocrine disruptors can affect the male germline epigenome by altering epigenetic reprogramming, but the mechanisms involved are still unknown. We have previously used an organ culture system that maintains the development of the different fetal testis cell types, to evaluate the effects of various endocrine disruptors on gametogenesis and steroidogenesis in the rat...
2017: Epigenetics & Chromatin
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