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https://www.readbyqxmd.com/read/28531272/a-novel-isoform-of-tet1-that-lacks-a-cxxc-domain-is-overexpressed-in-cancer
#1
Charly R Good, Jozef Madzo, Bela Patel, Shinji Maegawa, Nora Engel, Jaroslav Jelinek, Jean-Pierre J Issa
TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine (5hmC), resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1FL) has a CXXC domain that binds to unmethylated CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation, but it also limits its ability to regulate genes outside of CGIs. Here, we report a novel isoform of TET1 (TET1ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529766/genome-wide-profiling-of-dna-5-hydroxymethylcytosine-during-rat-sertoli-cell-maturation
#2
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/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#3
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28524723/l1-retrotransposition-is-activated-by-ten-eleven-translocation-protein-1-and-repressed-by-methyl-cpg-binding-proteins
#4
Peng Zhang, Anne K Ludwig, Florian D Hastert, Cathia Rausch, Anne Lehmkuhl, Ines Hellmann, Martha Smets, Heinrich Leonhardt, M Cristina Cardoso
One of the major functions of DNA methylation is the repression of transposable elements, such as the long-interspersed nuclear element 1 (L1). The underlying mechanism(s), however, are unclear. Here, we addressed how retrotransposon activation and mobilization are regulated by methyl-cytosine modifying ten-eleven-translocation (Tet) proteins and how this is modulated by methyl-CpG binding domain (MBD) proteins. We show that Tet1 activates both, endogenous and engineered L1 retrotransposons. Furthermore, we found that Mecp2 and Mbd2 repress Tet1-mediated activation of L1 by preventing 5hmC formation at the L1 promoter...
May 19, 2017: Nucleus
https://www.readbyqxmd.com/read/28520399/an-immunofluorescence-imaging-strategy-for-evaluation-of-the-accessibility-of-dna-5-hydroxymethylcytosine-in-chromatins
#5
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 to the abundance and distribution of DNA 5hmC in single cells. However, nuclear DNA is usually wrapped around nucleosomes and 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...
May 18, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#6
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28499883/the-role-of-5-hydroxymethylcytosine-in-development-aging-and-age-related-diseases
#7
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/28497329/effect-of-cadmium-on-cytosine-hydroxymethylation-in-gastropod-hepatopancreas
#8
Dragos Nica, Cristina Popescu, George Draghici, Ionela Privistirescu, Maria Suciu, Reinhard Stöger
5-Hydroxymethylcytosine (5hmC) is an important, yet poorly understood epigenetic DNA modification, especially in invertebrates. Aberrant genome-wide 5hmC levels have been associated with cadmium (Cd) exposure in humans, but such information is lacking for invertebrate bioindicators. Here, we aimed to determine whether this epigenetic mark is present in DNA of the hepatopancreas of the land snail Cantareus aspersus and is responsive to Cd exposure. Adult snails were reared under laboratory conditions and exposed to graded amounts of dietary cadmium for 14 days...
May 11, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28485726/gene-body-5-hydroxymethylation-is-associated-with-gene-expression-changes-in-the-prefrontal-cortex-of-depressed-individuals
#9
J A Gross, A Pacis, G G Chen, M Drupals, P-E Lutz, L B Barreiro, G Turecki
5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19)...
May 9, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28457889/2i-maintains-a-naive-ground-state-in-escs-through-two-distinct-epigenetic-mechanisms
#10
Ye-Ji Sim, Min-Seong Kim, Abeer Nayfeh, Ye-Jin Yun, Su-Jin Kim, Kyung-Tae Park, Chang-Hoon Kim, Kye-Seong Kim
Mouse embryonic stem cells (ESCs) are maintained in serum with leukemia inhibitory factor (LIF) to maintain self-renewal and pluripotency. Recently, a 2i culture method was reported using a combination of MEK inhibition (MEKi) and GSK3 inhibition (GSK3i) with LIF to maintain ESCs in a naive ground state. How 2i maintains a ground state of ESCs remains elusive. Here we show that MEKi and GSK3i maintain the ESC ground state by downregulating global DNA methylation through two distinct mechanisms. MEK1 phosphorylates JMJD2C for ubiquitin-mediated protein degradation...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28433420/dna-methylation-program-in-normal-and-alcohol-induced-thinning-cortex
#11
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
#12
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/28409505/dynamic-changes-in-dna-demethylation-in-the-tree-shrew-tupaia-belangeri-chinensis-brain-during-postnatal-development-and-aging
#13
Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum...
March 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28408905/tet-methylcytosine-oxidases-in-t-cell-and-b-cell-development-and-function
#14
REVIEW
Ageliki Tsagaratou, Chan-Wang J Lio, Xiaojing Yue, Anjana Rao
DNA methylation is established by DNA methyltransferases and is a key epigenetic mark. Ten-eleven translocation (TET) proteins are enzymes that oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidization products (oxi-mCs), which indirectly promote DNA demethylation. Here, we provide an overview of the effect of TET proteins and altered DNA modification status in T and B cell development and function. We summarize current advances in our understanding of the role of TET proteins and 5hmC in T and B cells in both physiological and pathological contexts...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28396520/cytosine-modifications-modulate-the-chromatin-architecture-of-transcriptional-enhancers
#15
Elise A Mahé, Thierry Madigou, Aurélien A Sérandour, Maud Bizot, Stéphane Avner, Frédéric Chalmel, Gaëlle Palierne, Raphaël Métivier, Gilles Salbert
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten Eleven Translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive...
April 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28348165/combinatorial-dna-methylation-codes-at-repetitive-elements
#16
Christophe Papin, Abdulkhaleg Ibrahim, Stephanie Le Gras, Amandine Velt, Bernard Jost, Isabelle Stoll, Hervé Menoni, Christian Bronner, Stefan Dimitrov, Ali Hamiche
DNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs...
March 27, 2017: Genome Research
https://www.readbyqxmd.com/read/28346420/hepatic-cyclooxygenase-2-overexpression-induced-spontaneous-hepatocellular-carcinoma-formation-in-mice
#17
H Chen, W Cai, E S H Chu, J Tang, C-C Wong, S H Wong, W Sun, Q Liang, J Fang, Z Sun, J Yu
Cyclooxygenase (COX)-2 is upregulated in hepatocellular carcinoma (HCC). However, the direct causative effect of COX-2 in spontaneous HCC formation remains unknown. We thus investigate the role and molecular pathogenesis of COX-2 in HCC by using liver-specific COX-2 transgenic (TG) mice. We found spontaneous HCC formation with elevated inflammatory infiltrates and neovessels in male TG mice (3/21, 14.3%), but not in any of male WT mice (0/19). Reduced representation bisulfite sequencing (RRBS) and gene expression microarrays were performed in the HCC tumor and non-HCC liver tissues to investigate the molecular mechanisms of COX-2-driven HCC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28332209/quantitation-and-mapping-of-the-epigenetic-marker-5-hydroxymethylcytosine
#18
Ying Qing, Zhiqi Tian, Ying Bi, Yongyao Wang, Jiangang Long, Chun-Xiao Song, Jiajie Diao
We here review primary methods used in quantifying and mapping 5-hydroxymethylcytosine (5hmC), including global quantification, restriction enzyme-based detection, and methods involving DNA-enrichment strategies and the genome-wide sequencing of 5hmC. As discovered in the mammalian genome in 2009, 5hmC, oxidized from 5-methylcytosine (5mC) by ten-eleven translocation (TET) dioxygenases, is increasingly being recognized as a biomarker in biological processes from development to pathogenesis, as its various detection methods have shown...
March 23, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28325772/tet3-mediated-dna-oxidation-promotes-atr-dependent-dna-damage-response
#19
Dewei Jiang, Shu Wei, Fei Chen, Ying Zhang, Jiali Li
An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death...
May 2017: EMBO Reports
https://www.readbyqxmd.com/read/28322935/early-pathogenesis-during-infectious-bursal-disease-in-susceptible-chickens-is-associated-with-changes-in-b-cell-genomic-methylation-and-loss-of-genome-integrity
#20
Nick A Ciccone, Lorraine P Smith, William Mwangi, Amy Boyd, Andrew J Broadbent, Adrian L Smith, Venugopal Nair
We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS...
August 2017: Developmental and Comparative Immunology
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