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active DNA demethylation

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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/28512237/regulation-of-dna-demethylation-by-the-xpc-dna-repair-complex-in-somatic-and-pluripotent-stem-cells
#2
Jaclyn J Ho, Claudia Cattoglio, David T McSwiggen, Robert Tjian, Yick W Fong
Faithful resetting of the epigenetic memory of a somatic cell to a pluripotent state during cellular reprogramming requires DNA methylation to silence somatic gene expression and dynamic DNA demethylation to activate pluripotency gene transcription. The removal of methylated cytosines requires the base excision repair enzyme TDG, but the mechanism by which TDG-dependent DNA demethylation occurs in a rapid and site-specific manner remains unclear. Here we show that the XPC DNA repair complex is a potent accelerator of global and locus-specific DNA demethylation in somatic and pluripotent stem cells...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28507144/critical-roles-of-dna-demethylation-in-the-activation-of-ripening-induced-genes-and-inhibition-of-ripening-repressed-genes-in-tomato-fruit
#3
Zhaobo Lang, Yihai Wang, Kai Tang, Dengguo Tang, Tatsiana Datsenka, Jingfei Cheng, Yijing Zhang, Avtar K Handa, Jian-Kang Zhu
DNA methylation is a conserved epigenetic mark important for genome integrity, development, and environmental responses in plants and mammals. Active DNA demethylation in plants is initiated by a family of 5-mC DNA glycosylases/lyases (i.e., DNA demethylases). Recent reports suggested a role of active DNA demethylation in fruit ripening in tomato. In this study, we generated loss-of-function mutant alleles of a tomato gene, SlDML2, which is a close homolog of the Arabidopsis DNA demethylase gene ROS1 In the fruits of the tomato mutants, increased DNA methylation was found in thousands of genes...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28504700/lineage-specific-functions-of-tet1-in-the-postimplantation-mouse-embryo
#4
Rita Khoueiry, Abhishek Sohni, Bernard Thienpont, Xinlong Luo, Joris Vande Velde, Michela Bartoccetti, Bram Boeckx, An Zwijsen, Anjana Rao, Diether Lambrechts, Kian Peng Koh
The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are not detectably expressed. TET1 regulates numerous genes defining differentiation programs in the epiblast and extraembryonic ectoderm...
May 15, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#5
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28498365/inhibition-of-twist1-mediated-invasion-by-chk2-promotes-premature-senescence-in-p53-defective-cancer-cells
#6
Debasis Nayak, Anmol Kumar, Souneek Chakraborty, Reyaz Ur Rasool, Hina Amin, Archana Katoch, Veena Gopinath, Vidushi Mahajan, Mahesh K Zilla, Bilal Rah, Sumit G Gandhi, Asif Ali, Lekha Dinesh Kumar, Anindya Goswami
Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28494938/pi3k-akt-mtor-signaling-mediates-valproic-acid-induced-neuronal-differentiation-of-neural-stem-cells-through-epigenetic-modifications
#7
Xi Zhang, Xiaosong He, Qingqing Li, Xuejian Kong, Zhenri Ou, Le Zhang, Zhuo Gong, Dahong Long, Jianhua Li, Meng Zhang, Weidong Ji, Wenjuan Zhang, Liping Xu, Aiguo Xuan
Although valproic acid (VPA), has been shown to induce neuronal differentiation of neural stem cells (NSCs), the underlying mechanisms remain poorly understood. Here we investigated if and how mammalian target of rapamycin (mTOR) signaling is involved in the neuronal differentiation of VPA-induced NSCs. Our data demonstrated that mTOR activation not only promoted but also was necessary for the neuronal differentiation of NSCs induced by VPA. We further found that inhibition of mTOR signaling blocked demethylation of neuron-specific gene neurogenin 1 (Ngn1) regulatory element in induced cells...
May 9, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28487730/the-methylation-status-and-expression-of-epstein-barr-virus-early-genes-barf1-and-bhrf1-in-epstein-barr-virus-associated-gastric-carcinomas
#8
Jing Li, Wen Liu, Kui Che, Yan Zhang, Zhenzhen Zhao, Bing Luo
Epstein-Barr virus (EBV) is an important DNA virus which establishes latent infection in human malignancies. Expression of EBV-encoded genes in the associated tumors is strongly modulated by promoter CpG methylation of EBV genome. This study aimed to explore the methylation status of the promoters of EBV BamHI-A rightward frame 1 (BARF1) and BamHI-H rightward open reading frame 1 (BHRF1) and their influence on transcriptional expression, to further understand the roles of BARF1 and BHRF1 in the occurrence of EBV-associated cancer...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28481873/restoring-pu-1-induces-apoptosis-and-modulates-viral-transactivation-via-interferon-stimulated-genes-in-primary-effusion-lymphoma
#9
H Goto, R Kariya, E Kudo, Y Okuno, K Ueda, H Katano, S Okada
Primary effusion lymphoma (PEL), which is an aggressive subgroup of B-cell lymphoma associated with Kaposi sarcoma-associated herpes virus/human herpes virus-8, is refractory to the standard treatment, and exhibits a poor survival. Although PU.1 is downregulated in PEL, the potential role of its reduction remains to be elucidated. In this investigation, we analyzed the DNA methylation of PU.1 cis-regulatory elements in PEL and the effect of restoring PU.1 on PEL cells. The mRNA level of PU.1 was downregulated in PEL cells...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28479091/family-wide-comparative-analysis-of-cytidine-and-methylcytidine-deamination-by-eleven-human-apobec-proteins
#10
Fumiaki Ito, Yang Fu, Shen-Chi A Kao, Hanjing Yang, Xiaojiang S Chen
APOBECs are a family of cytidine deaminases involved in various important biological processes such as antibody diversification/maturation, restriction of viral infection, and generation of somatic mutations. Catalytically active APOBEC proteins execute their biological functions mostly through deaminating cytosine (C) to uracil on ssDNA/RNA. Activation-induced cytidine deaminase (AID), one of the APOBEC members, was reported to deaminate methylated cytosine (mC) on DNA and this mC deamination was proposed to be involved in demethylation of mC for epigenetic regulation...
May 4, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28472485/apobec3a-efficiently-deaminates-methylated-but-not-tet-oxidized-cytosine-bases-in-dna
#11
Emily K Schutsky, Christopher S Nabel, Amy K F Davis, Jamie E DeNizio, Rahul M Kohli
AID/APOBEC family enzymes are best known for deaminating cytosine bases to uracil in single-stranded DNA, with characteristic sequence preferences that can produce mutational signatures in targets such as retroviral and cancer cell genomes. These deaminases have also been proposed to function in DNA demethylation via deamination of either 5-methylcytosine (mC) or TET-oxidized mC bases (ox-mCs), which include 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. One specific family member, APOBEC3A (A3A), has been shown to readily deaminate mC, raising the prospect of broader activity on ox-mCs...
May 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28470479/epigenetic-variability-in-systemic-lupus-erythematosus-what-we-learned-from-genome-wide-dna-methylation-studies
#12
REVIEW
Maria Teruel, Amr H Sawalha
PURPOSE OF REVIEW: DNA methylation has emerged as an important contributing factor in the pathogenesis of systemic lupus erythematosus (SLE). Here, we describe the DNA methylation patterns identified in SLE and how these epigenetic changes can influence disease susceptibility, clinical heterogeneity, and disease flares. RECENT FINDINGS: Several genome-wide DNA methylation studies have been recently completed in SLE. Important observations include robust demethylation of interferon-regulated genes, which is consistent across all cell types studied to date, and is independent of disease activity...
June 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28467815/epigenetic-silencing-of-triple-negative-breast-cancer-hallmarks-by-withaferin-a
#13
Katarzyna Szarc Vel Szic, Ken Declerck, René A J Crans, Jolien Diddens, David B Scherf, Clarissa Gerhäuser, Wim Vanden Berghe
Triple negative breast cancer (TNBC) is characterized by poor prognosis and a DNA hypomethylation profile. Withaferin A (WA) is a plant derived steroidal lactone which holds promise as a therapeutic agent for treatment of breast cancer (BC). We determined genome-wide DNA methylation changes in weakly-metastatic and aggressive, metastatic BC cell lines, following 72h treatment to a sub-cytotoxic concentration of WA. In contrast to the DNA demethylating agent 5-aza-2'-deoxycytidine (DAC), WA treatment of MDA-MB-231 cells rather tackles an epigenetic cancer network through gene-specific DNA hypermethylation of tumor promoting genes including ADAM metallopeptidase domain 8 (ADAM8), urokinase-type plasminogen activator (PLAU), tumor necrosis factor (ligand) superfamily, member 12 (TNFSF12), and genes related to detoxification (glutathione S-transferase mu 1, GSTM1), or mitochondrial metabolism (malic enzyme 3, ME3)...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28461979/search-for-modified-dna-sites-with-the-human-methyl-cpg-binding-enzyme-mbd4
#14
D A Yakovlev, A A Kuznetsova, O S Fedorova, N A Kuznetsov
The MBD4 enzyme initiates the process of DNA demethylation by the excision of modified DNA bases, resulting in the formation of apurinic/apyrimidinic sites. MBD4 contains a methyl-CpG-binding domain which provides the localization of the enzyme at the CpG sites, and a DNA glycosylase domain that is responsible for the catalytic activity. The aim of this work was to clarify the mechanisms of specific site recognition and formation of catalytically active complexes between model DNA substrates and the catalytic N-glycosylase domain MBD4cat...
January 2017: Acta Naturae
https://www.readbyqxmd.com/read/28460463/set-oncoprotein-accumulation-regulates-transcription-through-dna-demethylation-and-histone-hypoacetylation
#15
Luciana O Almeida, Marinaldo P C Neto, Lucas O Sousa, Maryna A Tannous, Carlos Curti, Andreia M Leopoldino
Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453518/lc-ms-ms-quantitative-analysis-reveals-the-association-between-fto-and-dna-methylation
#16
Yuting Zhu, Guangyu Zhou, Xuebin Yu, Qiang Xu, Kai Wang, Dan Xie, Qingkai Yang, Lina Wang
Fat mass and obesity-associated protein (FTO) is α-ketoglutarate-dependent dioxygenase and responsible for demethylating N6-methyladenosine (m6A) in mRNA, 3-methylthymine (m3T) in single-stranded DNA (ssDNA) and 3-methyluracil (m3U) in single-stranded RNA (ssRNA). Its other function remains unknown but thousands of mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC) modification and 5mdC demethylases are required for mammalian energy homeostasis and fertility. Here, we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28453190/synergistic-activity-of-everolimus-and-5-aza-2-deoxycytidine-in-medullary-thyroid-carcinoma-cell-lines
#17
Giovanni Vitale, Alessandra Dicitore, Daniele Pepe, Davide Gentilini, Elisa Stellaria Grassi, Maria Orietta Borghi, Giulia Gelmini, Maria Celeste Cantone, Germano Gaudenzi, Gabriella Misso, Anna Maria Di Blasio, Leo J Hofland, Michele Caraglia, Luca Persani
Medullary thyroid cancer (MTC) is a tumor highly resistant to chemo- and radiotherapy. Drug resistance can be induced by epigenetic changes such as aberrant DNA methylation. To overcome drug resistance, we explored a promising approach based on the use of 5-aza-2'-deoxycytidine (AZA), a demethylating agent, in combination with the mTOR inhibitor everolimus in MTC cells (MZ-CRC-1 and TT). This combined treatment showed a strong synergistic antiproliferative activity through the induction of apoptosis. The effect of everolimus and/or AZA on genome-wide expression profiling was evaluated by Illumina BeadChip in MZ-CRC-1 cells...
April 28, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28444170/neuronal-activity-tgf%C3%AE-signaling-and-unpredictable-chronic-stress-modulate-transcription-of-gadd45-family-members-and-dna-methylation-in-the-hippocampus
#18
Daniela Grassi, Henriette Franz, Riccardo Vezzali, Patrick Bovio, Stefanie Heidrich, Fariba Dehghanian, Natalia Lagunas, Catherine Belzung, Kerstin Krieglstein, Tanja Vogel
Neuronal activity is altered in several neurological and psychiatric diseases. Upon depolarization not only neurotransmitters are released but also cytokines and other activators of signaling cascades. Unraveling their complex implication in transcriptional control in receiving cells will contribute to understand specific central nervous system (CNS) pathologies and will be of therapeutically interest. In this study we depolarized mature hippocampal neurons in vitro using KCl and revealed increased release not only of brain-derived neurotrophic factor (BDNF) but also of transforming growth factor beta (TGFB)...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28436623/mthfr-methylation-moderates-the-impact-of-smoking-on-dna-methylation-at-ahrr-for-african-american-young-adults
#19
Steven R H Beach, Man Kit Lei, Mei Ling Ong, Gene H Brody, Meeshanthini V Dogan, Robert A Philibert
Smoking has been shown to have a large, reliable, and rapid effect on demethylation of AHRR, particularly at cg05575921, suggesting that methylation may be used as an index of cigarette consumption. Because the availability of methyl donors may also influence the degree of demethylation in response to smoking, factors that affect the activity of methylene tetrahydrofolate reductase (MTHFR), a key regulator of methyl group availability, may be of interest. In the current investigation, we examined the extent to which individual differences in methylation of MTHFR moderated the association between smoking and demethylation at cg05575921 as well as at other loci on AHRR associated with a main effect of smoking...
April 24, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28431504/erratum-to-runx1-induces-dna-replication-independent-active-dna-demethylation-at-spi1-regulatory-regions
#20
Shubham Goyal, Takahiro Suzuki, Jing-Ru Li, Shiori Maeda, Mami Kishima, Hajime Nishimura, Yuri Shimizu, Harukazu Suzuki
No abstract text is available yet for this article.
April 21, 2017: BMC Molecular Biology
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