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Histone demethylation

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https://www.readbyqxmd.com/read/27902763/temperature-shift-alters-dna-methylation-and-histone-modification-patterns-in-gonadal-aromatase-cyp19a1-gene-in-species-with-temperature-dependent-sex-determination
#1
Yuiko Matsumoto, Brette Hannigan, David Crews
The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development...
2016: PloS One
https://www.readbyqxmd.com/read/27900345/new-insight-into-lsd1-function-in-human-cortical-neurogenesis
#2
Kazumi Hirano, Masakazu Namihira
The cerebral cortex of primates has evolved massively and intricately in comparison to that of other species. Accumulating evidence indicates that this is caused by changes in cell biological features of neural stem cells (NSCs), which differentiate into neurons and glial cells during development. The fate of NSCs during rodent cortical development is stringently regulated by epigenetic factors, such as histone modification enzymes, but the role of these factors in human corticogenesis is largely unknown. We have recently discovered that a lysine-specific demethylase 1 (LSD1), which catalyzes the demethylation of methyl groups in the histone tail, plays a unique role in human fetal NSCs (hfNSCs)...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27899639/histone-demethylase-phf8-promotes-epithelial-to-mesenchymal-transition-and-breast-tumorigenesis
#3
Peng Shao, Qi Liu, Peterson Kariuki Maina, Jiayue Cui, Thomas B Bair, Tiandao Li, Shaikamjad Umesalma, Weizhou Zhang, Hank Heng Qi
Histone demethylase PHF8 is upregulated and plays oncogenic roles in various cancers; however, the mechanisms underlying its dysregulation and functions in carcinogenesis remain obscure. Here, we report the novel functions of PHF8 in EMT (epithelial to mesenchymal transition) and breast cancer development. Genome-wide gene expression analysis revealed that PHF8 overexpression induces an EMT-like process, including the upregulation of SNAI1 and ZEB1. PHF8 demethylates H3K9me1, H3K9me2 and sustains H3K4me3 to prime the transcriptional activation of SNAI1 by TGF-β signaling...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27897198/mitochondrial-control-through-nutritionally-regulated-global-histone-h3-lysine-4-demethylation
#4
Maria Soloveychik, Mengshu Xu, Olga Zaslaver, Kwanyin Lee, Ashrut Narula, River Jiang, Adam P Rosebrock, Amy A Caudy, Marc D Meneghini
Histone demethylation by Jumonji-family proteins is coupled with the decarboxylation of α-ketoglutarate (αKG) to yield succinate, prompting hypotheses that their activities are responsive to levels of these metabolites in the cell. Consistent with this paradigm we show here that the Saccharomyces cerevisiae Jumonji demethylase Jhd2 opposes the accumulation of H3K4me3 in fermenting cells only when they are nutritionally manipulated to contain an elevated αKG/succinate ratio. We also find that Jhd2 opposes H3K4me3 in respiratory cells that do not exhibit such an elevated αKG/succinate ratio...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#5
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27876670/a-model-of-dynamic-stability-of-h3k9me3-heterochromatin-to-explain-the-resistance-to-reprogramming-of-differentiated-cells
#6
Charly Jehanno, Gilles Flouriot, Pascale Le Goff, Denis Michel
Despite their dynamic nature, certain chromatin marks must be maintained over the long term. This is particulary true for histone 3 lysine 9 (H3K9) trimethylation, that is involved in the maintenance of healthy differentiated cellular states by preventing inappropriate gene expression, and has been recently identified as the most efficient barrier to cellular reprogramming in nuclear transfer experiments. We propose that the capacity of the enzymes SUV39H1/2 to rebind to a minor fraction of their products, either directly or via HP1α/β, contributes to the solidity of this mark through (i) a positive feedback involved in its establishment by the mutual enforcement of H3K9me3 and SUV39H1/2 and then (ii) a negative feedback sufficient to strongly stabilize H3K9me3 heterochromatin in post-mitotic cells by generating local enzyme concentrations capable of counteracting transient bursts of demethylation...
November 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27863907/evidence-of-epigenetic-tags-in-cardiac-fibrosis
#7
REVIEW
Vincenzo Grimaldi, Maria Rosaria De Pascale, Alberto Zullo, Andrea Soricelli, Teresa Infante, Francesco Paolo Mancini, Claudio Napoli
In cardiac fibrosis, following an injury or a stress, non-functional fibrotic tissue substitutes normal myocardium, thus leading to progressive heart failure. Activated fibroblasts are principal determinants of cardiac fibrosis by producing excessive fibrotic extracellular matrix and causing hypertrophy of cardiomyocytes. Epigenetic changes, such as DNA methylation, histone modifications, and miRNAs have been involved in these mechanisms. Therefore, there is a strong interest in reverting such epigenetic transformations in order to arrest myocardial fibrotic degeneration...
November 15, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/27818689/epigenetic-remodeling-in-male-germline-development
#8
REVIEW
Na Li, Qiaoyan Shen, Jinlian Hua
In mammals, germ cells guarantee the inheritance of genetic and epigenetic information across generations and are the origin of a new organism. During embryo development, the blastocyst is formed in the early stage, is comprised of an inner cell mass which is pluripotent, and could give rise to the embryonic stem cells (ESCs). The inner cell mass undergoes demethylation processes and will reestablish a methylated state that is similar to that of somatic cells later in epiblast stage. Primordial germ cells (PGCs) will be formed very soon and accompanied by the process of genome-wide demethylation...
2016: Stem Cells International
https://www.readbyqxmd.com/read/27818231/epigenetic-reactivation-of-rassf1a-by-phenethyl-isothiocyanate-peitc-and-promotion-of-apoptosis-in-lncap-cells
#9
Sarandeep S S Boyanapalli, Wenji Li, Francisco Fuentes, Yue Guo, Christina N Ramirez, Ximena-Parades Gonzalez, Douglas Pung, Ah-Ng Tony Kong
Epigenetic silencing of tumor suppressor genes is a phenomenon frequently observed in multiple cancers. Ras-association domain family 1 isoform A (RASSF1A) is a well-characterized tumor suppressor that belongs to the Ras-association domain family. Several studies have demonstrated that hypermethylation of the RASSF1A promoter is frequently observed in lung, prostate, and breast cancers. Phenethyl isothiocyanate (PEITC), a phytochemical abundant in cruciferous vegetables, possesses chemopreventive activities; however, its potential involvement in epigenetic mechanisms remains elusive...
November 3, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27813113/promoter-cpg-site-methylation-of-the-kai1-metastasis-suppressor-gene-contributes-to-its-epigenetic-repression-in-prostate-cancer
#10
Jaeseob Lee, Moon-Sung Lee, Doo-Il Jeoung, Young-Myeong Kim, Hansoo Lee
BACKGROUND: Repression of the KAI1 metastasis suppressor gene is closely associated with malignancy and poor prognosis in many human cancer types including prostate cancer. Since gene repression in human cancers frequently results from epigenetic alterations by DNA methylation and histone modifications, we examined whether the KAI1 gene becomes silenced through these epigenetic mechanisms in prostate cancer. METHODS: KAI1 mRNA and protein levels were determined by RT-PCR and immunoblotting analyses, respectively...
November 3, 2016: Prostate
https://www.readbyqxmd.com/read/27802135/transient-ectopic-expression-of-the-histone-demethylase-jmjd3-accelerates-the-differentiation-of-human-pluripotent-stem-cells
#11
Tomohiko Akiyama, Shunichi Wakabayashi, Atsumi Soma, Saeko Sato, Yuhki Nakatake, Mayumi Oda, Miyako Murakami, Miki Sakota, Nana Chikazawa-Nohtomi, Shigeru B H Ko, Minoru S H Ko
Harnessing epigenetic regulation is crucial for the efficient and proper differentiation of pluripotent stem cells (PSCs) into desired cell types. Histone H3 lysine 27 trimethylation (H3K27me3) functions as a barrier against cell differentiation through the suppression of developmental gene expression in PSCs. Here, we have generated human PSC (hPSC) lines in which genome-wide reduction of H3K27me3 can be induced by ectopic expression of the catalytic domain of the histone demethylase JMJD3 (called JMJD3c)...
October 15, 2016: Development
https://www.readbyqxmd.com/read/27800026/hypoxia-increases-genome-wide-bivalent-epigenetic-marking-by-specific-gain-of-h3k27me3
#12
Peggy Prickaerts, Michiel E Adriaens, Twan van den Beucken, Elizabeth Koch, Ludwig Dubois, Vivian E H Dahlmans, Caroline Gits, Chris T A Evelo, Michelle Chan-Seng-Yue, Bradly G Wouters, Jan Willem Voncken
BACKGROUND: Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered microenvironmental conditions, including low-oxygen conditions commonly present in solid tumors, is relatively unknown. Demethylation of H3K4me3 and H3K27me3 is mediated by oxygen and 2-oxoglutarate dioxygenases enzymes, suggesting that oxygen deprivation (hypoxia) may influence histone trimethylation...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27798602/s-2-hydroxyglutarate-regulates-cd8-t-lymphocyte-fate
#13
Petros A Tyrakis, Asis Palazon, David Macias, Kian L Lee, Anthony T Phan, Pedro Veliça, Jia You, Grace S Chia, Jingwei Sim, Andrew Doedens, Alice Abelanet, Colin E Evans, John R Griffiths, Lorenz Poellinger, Ananda W Goldrath, Randall S Johnson
R-2-hydroxyglutarate accumulates to millimolar levels in cancers with gain-of-function isocitrate dehydrogenase 1/2 mutations. These levels of R-2-hydroxyglutarate affect 2-oxoglutarate-dependent dioxygenases. Both R- and S-2-hydroxyglutarate, the other enantiomer of this metabolite, are detectible in healthy individuals, yet their physiological function remains elusive. Here we show that CD8(+) T-lymphocytes accumulate 2-hydroxyglutarate in response to T-cell receptor triggering. This increases to millimolar levels in physiological oxygen conditions, via a hypoxia inducible factor 1 alpha-dependent mechanism...
October 26, 2016: Nature
https://www.readbyqxmd.com/read/27742770/inhibition-of-demethylase-kdm6b-sensitizes-diffuse-large-b-cell-lymphoma-to-chemotherapeutic-drugs
#14
Rohit Mathur, Lalit Sehgal, Ondrej Havranek, Stefan Köhrer, Tamer Khashab, Neeraj Jain, Jan A Burger, Sattva S Neelapu, R Eric Davis, Felipe Samaniego
Histone methylation and demethylation regulates B-cell development, and their deregulation correlates with tumor chemoresistance in diffuse large B-cell lymphoma, limiting curative rates. Since histone methylation status correlates with disease aggressiveness and relapse, we investigated the therapeutic potential of inhibiting histone 3 Lys27 demethylase KDM6B, in-vitro, using the small molecule inhibitor GSK-J4. KDM6B is overexpressed in the DLBCL germinal center B-cell subtype, and higher KDM6B levels are associated with worse survival in DLBCL patients treated with R-CHOP...
October 14, 2016: Haematologica
https://www.readbyqxmd.com/read/27737935/whole-genome-analysis-of-the-methylome-and-hydroxymethylome-in-normal-and-malignant-lung-and-liver
#15
Xin Li, Yun Liu, Tal Salz, Kasper D Hansen, Andrew Feinberg
DNA methylation at the 5-position of cytosine (5mC) is an epigenetic modification that regulates gene expression and cellular plasticity in development and disease. The ten-eleven translocation (TET) gene family oxidizes 5mC to 5-hydroxymethylcytosine (5hmC), providing an active mechanism for DNA demethylation, and it may also provide its own regulatory function. Here we applied oxidative bisulfite sequencing to generate whole-genome DNA methylation and hydroxymethylation maps at single-base resolution in human normal liver and lung as well as paired tumor tissues...
October 13, 2016: Genome Research
https://www.readbyqxmd.com/read/27737800/hypoxic-inhibition-of-jmjd3-reduces-h3k27me3-demethylation-and-induction-of-the-stat6-target-gene-ccl18
#16
Nathalie Dehne, Bernhard Brüne
Hypoxia, by activating transcription factors induces transcription of some genes but it also reduces mRNA synthesis by mechanisms that are poorly defined. Activation of human macrophages with interleukin (IL)-4 showed that up-regulation of some IL-4 target genes was reduced when macrophages were incubated at 1% oxygen. Hypoxia impaired induction of chemokine (C-C motif) ligand 18 (CCL18), although IL-4-induced DNA binding of the transcription factor STAT6 remained intact. In contrast, induction of serine peptidase inhibitor, Kunitz type (SPINT)2, another IL-4/STAT6 target gene, was not affected by hypoxia...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27735137/lysyl-oxidase-like-2-loxl2-oxidizes-trimethylated-lysine-4-in-histone-h3
#17
Nicolás Herranz, Natàlia Dave, Alba Millanes-Romero, Laura Pascual, Lluis Morey, Víctor M Díaz, Víctor Lórenz-Fonfría, Ricardo Gutierrez-Gallego, Celia Jerónimo, Ane Iturbide, Luciano Di Croce, Antonio García de Herreros, Sandra Peiró
Methylation of histone H3 lysine 4 is linked to active transcription and can be removed by LSD1 or the JmjC domain-containing proteins by amino-oxidation or hydroxylation, respectively. Here we describe that its deamination can be catalyzed by lysyl oxidase-like 2 protein (LOXL2), presenting an unconventional chemical mechanism for H3K4 modification. Infrared spectroscopy and mass spectrometry analyses demonstrated that recombinant LOXL2 specifically deaminates trimethylated H3K4. Moreover, by regulating H3K4me3 deamination, LOXL2 activity is linked with the transcriptional control of the CDH1 gene...
October 13, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27733505/tet1-modulates-h4k16-acetylation-by-controlling-auto-acetylation-of-hmof-to-affect-gene-regulation-and-dna-repair-function
#18
Jianing Zhong, Xianfeng Li, Wanshi Cai, Yan Wang, Shanshan Dong, Jie Yang, Jian'an Zhang, Nana Wu, Yuanyuan Li, Fengbiao Mao, Cheng Zeng, Jinyu Wu, Xingzhi Xu, Zhong Sheng Sun
The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through altering statue of DNA methylation. However, recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; yet, the detailed mechanisms underlying TET1's role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets and a series of in vitro biochemical studies in human cell lines...
October 12, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27732873/systematic-analysis-of-known-and-candidate-lysine-demethylases-in-the-regulation-of-myoblast-differentiation
#19
Yoichi Munehira, Ze Yang, Or Gozani
Histone methylation dynamics plays a critical role in cellular programming during development. For example, specific lysine methyltransferases (KMTs) and lysine demethylases (KDMs) have been implicated in the differentiation of mesenchymal stem cells into various cell lineages. However, a systematic and functional analysis for an entire family of KMT or KDM enzymes has not been performed. Here, we test the function of all the known and candidate KDMs in myoblast and osteoblast differentiation using the C2C12 cell differentiation model system...
October 11, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27727500/two-state-reactivity-of-histone-demethylases-containing-jumonji-c-active-sites-different-mechanisms-for-different-methylation-degrees
#20
Nerea Alonso, Miquel Torrent-Sucarrat, Iosune Arrastia, Ana Arrieta, Fernando P Cossío
The N-demethylation reactions of N,N,N-trimethylpropan-1-ammonium and N,N-dimethyl-, and N-methylpropan-1-aminium cations in the presence of (AcO)2(imidazole)2(H2O)Fe=O complex have been studied by density functional theory. These transformations are suitable models for the N-demethylation of tri-, di-, and monomethylated lysine residues of histones in the presence of Jumonji-C containing histone demethylases. It has been found that the N-demethylation reaction is stepwise and occurs on triplet and quintet potential energy hypersurfaces...
October 11, 2016: Chemistry: a European Journal
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