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H3K27me3

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https://www.readbyqxmd.com/read/29791850/the-memory-of-environmental-chemical-exposure-in-c-elegans-is-dependent-on-the-jumonji-demethylases-jmjd-2-and-jmjd-3-utx-1
#1
Jessica Camacho, Lisa Truong, Zeyneb Kurt, Yen-Wei Chen, Marco Morselli, Gerardo Gutierrez, Matteo Pellegrini, Xia Yang, Patrick Allard
How artificial environmental cues are biologically integrated and transgenerationally inherited is still poorly understood. Here, we investigate the mechanisms of inheritance of reproductive outcomes elicited by the model environmental chemical Bisphenol A in C. elegans. We show that Bisphenol A (BPA) exposure causes the derepression of an epigenomically silenced transgene in the germline for 5 generations, regardless of ancestral response. Chromatin immunoprecipitation sequencing (ChIP-seq), histone modification quantitation, and immunofluorescence assays revealed that this effect is associated with a reduction of the repressive marks H3K9me3 and H3K27me3 in whole worms and in germline nuclei in the F3, as well as with reproductive dysfunctions, including germline apoptosis and embryonic lethality...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29791133/design-construction-and-validation-of-histone-binding-effectors-in-vitro-and-in-cells
#2
Stefan J Tekel, Cassandra M Barrett, Daniel A Vargas, Karmella A Haynes
Chromatin is a system of nuclear proteins and nucleic acids that plays a pivotal role in gene expression and cell behavior, and is therefore the subject of intense study for cell development and cancer research. Biochemistry, crystallography, and reverse genetics have elucidated the macromolecular interactions that drive chromatin regulation. One of the central mechanisms is the recognition of post translational modifications (PTMs) on histone proteins by a family of nuclear proteins known as "readers...
May 23, 2018: Biochemistry
https://www.readbyqxmd.com/read/29789597/enhancer-of-zeste-homolog-2-catalysed-h3k27-trimethylation-plays-a-key-role-in-acute-on-chronic-liver-failure-via-tnf-mediated-pathway
#3
Tianhui Zhou, Ye Sun, Ming Li, Yongsen Ding, Rongkun Yin, Ziqiang Li, Qing Xie, Shisan Bao, Wei Cai
Acute-on-chronic liver failure is mainly due to host immunity self-destruction. The histone H3 lysine 27 (H3K27) trimethylating enzyme, enhancer of zeste homolog 2 (EZH2) mediates epigenetic silencing of gene expression and regulates immunity, also involves pathogenesis of several liver diseases. The current study was to determine the role of methyltransferase EZH2 and its catalysed H3K27 trimethylation (H3K27me3) in liver failure, and to further investigate the potential target for liver failure treatment...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29788048/robustness-of-transposable-element-regulation-but-no-genomic-shock-observed-in-interspecific-arabidopsis-hybrids
#4
Ulrike Göbel, Agustin Arce, Fei He, Alain Rico, Gregor Schmitz, Juliette de Meaux
The merging of two divergent genomes in a hybrid is believed to trigger a "genomic shock", disrupting gene regulation and transposable element (TE) silencing. Here, we tested this expectation by comparing the pattern of expression of transposable elements in their native and hybrid genomic context. For this, we sequenced the transcriptome of the Arabidopsis thaliana genotype Col-0, the A. lyrata genotype MN47 and their F1 hybrid. Contrary to expectations, we observe that the level of TE expression in the hybrid is strongly correlated to levels in the parental species...
May 18, 2018: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29784958/polycomb-repressive-complex-2-attenuates-the-very-high-expression-of-the-arabidopsis-gene-nrt2-1
#5
Fanny Bellegarde, Léo Herbert, David Séré, Erwann Caillieux, Jossia Boucherez, Cécile Fizames, François Roudier, Alain Gojon, Antoine Martin
PRC2 is a major regulator of gene expression in eukaryotes. It catalyzes the repressive chromatin mark H3K27me3, which leads to very low expression of target genes. NRT2.1, which encodes a key root nitrate transporter in Arabidopsis, is targeted by H3K27me3, but the function of PRC2 on NRT2.1 remains unclear. Here, we demonstrate that PRC2 directly targets and down-regulates NRT2.1, but in a context of very high transcription, in nutritional conditions where this gene is one of the most highly expressed genes in the transcriptome...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#6
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29779894/epigenetic-regulation-by-baf-complexes-limits-neural-stem-cell-proliferation-by-suppressing-wnt-signaling-in-late-embryonic-development
#7
Huong Nguyen, Cemil Kerimoglu, Mehdi Pirouz, Linh Pham, Kamila A Kiszka, Godwin Sokpor, M Sadman Sakib, Joachim Rosenbusch, Ulrike Teichmann, Rho H Seong, Anastassia Stoykova, Andre Fischer, Jochen F Staiger, Tran Tuoc
During early cortical development, neural stem cells (NSCs) divide symmetrically to expand the progenitor pool, whereas, in later stages, NSCs divide asymmetrically to self-renew and produce other cell types. The timely switch from such proliferative to differentiative division critically determines progenitor and neuron numbers. However, the mechanisms that limit proliferative division in late cortical development are not fully understood. Here, we show that the BAF (mSWI/SNF) complexes restrict proliferative competence and promote neuronal differentiation in late corticogenesis...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#8
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29773426/stem-cell-transcription-factor-sox2-in-synovial-sarcoma-and-other-soft-tissue-tumors
#9
Heba Zayed, Iver Petersen
BACKGROUND: SOX2 has gained considerable interest as a pluripotency inducing gene. Co-transfection of SOX2 together with NANOG, KLF4 and c-MYC into adult fibroblasts was able to generate pluripotent stem cells. SOX2 has been reported to be expressed in synovial sarcoma, a tumor being characterized by the SS18-SSX gene fusion forming part of the SWI/SNF chromatin remodeling complex that affects histone methylation. The role of SOX2 in this tumor type as well as other soft tissue tumor entities however is still poorly characterized...
May 4, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29768655/let-7e-inhibits-tnf-%C3%AE-expression-by-targeting-the-methyl-transferase-ezh2-in-denv2-infected-thp-1-cells
#10
Yingke Zhang, Qianqian Zhang, Lian Gui, Yan Cai, Xiaohong Deng, Cheukfai Li, Qi Guo, Xiaoshun He, Junqi Huang
Tumor necrosis factor α (TNFα), an important inflammatory cytokine, is associated with dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), a severe pathological manifestation of dengue virus (DENV) infection. However, the regulatory mechanism of microRNA on TNFα is currently unknown. Our study showed that the TNFα expression increased immediately and then later decreased, while a marked increase for the miRNA let-7e was detected in dengue virus type 2 (DENV2)-infected peripheral blood mononuclear cells (PBMCs)...
May 16, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29765032/pcgf5-is-required-for-neural-differentiation-of-embryonic-stem-cells
#11
Mingze Yao, Xueke Zhou, Jiajian Zhou, Shixin Gong, Gongcheng Hu, Jiao Li, Kaimeng Huang, Ping Lai, Guang Shi, Andrew P Hutchins, Hao Sun, Huating Wang, Hongjie Yao
Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29765031/comprehensive-epigenetic-landscape-of-rheumatoid-arthritis-fibroblast-like-synoviocytes
#12
Rizi Ai, Teresina Laragione, Deepa Hammaker, David L Boyle, Andre Wildberg, Keisuke Maeshima, Emanuele Palescandolo, Vinod Krishna, David Pocalyko, John W Whitaker, Yuchen Bai, Sunil Nagpal, Kurtis E Bachman, Richard I Ainsworth, Mengchi Wang, Bo Ding, Percio S Gulko, Wei Wang, Gary S Firestein
Epigenetics contributes to the pathogenesis of immune-mediated diseases like rheumatoid arthritis (RA). Here we show the first comprehensive epigenomic characterization of RA fibroblast-like synoviocytes (FLS), including histone modifications (H3K27ac, H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3), open chromatin, RNA expression and whole-genome DNA methylation. To address complex multidimensional relationship and reveal epigenetic regulation of RA, we perform integrative analyses using a novel unbiased method to identify genomic regions with similar profiles...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29760161/ctcf-boundary-remodels-chromatin-domain-and-drives-aberrant-hox-gene-transcription-in-acute-myeloid-leukemia
#13
Huacheng Luo, Fei Wang, Jie Zha, Haoli Li, Bowen Yan, Qinghua Du, Fengchun Yang, Amin Sobh, Christopher Vulpe, Leylah Drusbosky, Christopher Cogle, Iouri Chepelev, Bing Xu, Stephen D Nimer, Jonathan Licht, Yi Qiu, Baoan Chen, Mingjiang Xu, Suming Huang
HOX gene dysregulation is a common feature of acute myeloid leukemia (AML). The molecular mechanisms underlying aberrant HOX gene expression and associated AML pathogenesis remain unclear. The nuclear protein CCCTC-binding factor (CTCF), when bound to insulator sequences, constrains temporal HOX gene expression patterns within confined chromatin domains for normal development. Here, we employed targeted pooled CRISPR-Cas9 knockout library screening to interrogate the function of CTCF boundaries in the HOX gene loci...
May 14, 2018: Blood
https://www.readbyqxmd.com/read/29755682/evaluation-of-the-impact-of-s-adenosylmethionine-dependent-methyltransferase-inhibitor-3-deazaneplanocin-a-on-tissue-injury-and-cognitive-function-in-mice
#14
Eva Lhuissier, Juliette Aury-Landas, Valentine Bouet, Céline Bazille, Yohann Repesse, Thomas Freret, Karim Boumédiene, Catherine Baugé
Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients' quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755673/role-of-epigenetic-factors-in-the-selection-of-the-alternative-splicing-isoforms-of-human-kras-in-colorectal-cancer-cell-lines
#15
Ángela L Riffo-Campos, Francisco Gimeno-Valiente, Fernanda M Rodríguez, Andrés Cervantes, Gerardo López-Rodas, Luis Franco, Josefa Castillo
Mutation-driven activation of KRAS is crucial to cancer development. The human gene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Their different properties and oncogenic potential have been studied, but the mechanisms deciding the ratio 4A/4B are not known. To address this issue, the expression of the four KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116 and SW48 were further selected because they present the highest difference in the ratio 4A/4B (twice as much in HCT116 than in SW48)...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753027/jmjd3-inhibition-protects-against-isoproterenol-induced-cardiac-hypertrophy-by-suppressing-%C3%AE-mhc-expression
#16
Zhen Guo, Jing Lu, Jingyan Li, Panxia Wang, Zhenzhen Li, Yao Zhong, Kaiteng Guo, Junjian Wang, Jiantao Ye, Peiqing Liu
Jumonji domain-containing protein D3 (JMJD3), a histone 3 lysine 27 (H3K27) demethylase, has been extensively studied for their participation in development, cellular physiology and a variety of diseases. However, its potential roles in cardiovascular system remain unknown. In this study, we found that JMJD3 played a pivotal role in the process of cardiac hypertrophy. JMJD3 expression was elevated by isoproterenol (ISO) stimuli both in vitro and in vivo. Overexpression of wild-type JMJD3, but not the demethylase-defective mutant, promoted cardiomyocyte hypertrophy, as implied by increased cardiomyocyte surface area and the expression of hypertrophy marker genes...
May 9, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29752431/ddb2-represses-ovarian-cancer-cell-dedifferentiation-by-suppressing-aldh1a1
#17
Tiantian Cui, Amit Kumar Srivastava, Chunhua Han, Dayong Wu, Nissar Wani, Lu Liu, Zhiqin Gao, Meihua Qu, Ning Zou, Xiaoli Zhang, Ping Yi, Jianhua Yu, Erica H Bell, Shyh-Ming Yang, David J Maloney, Yanfang Zheng, Altaf A Wani, Qi-En Wang
Cancer stem cells (CSCs), representing the root of many solid tumors including ovarian cancer, have been implicated in disease recurrence, metastasis, and therapeutic resistance. Our previous study has demonstrated that the CSC subpopulation in ovarian cancer can be limited by DNA damage-binding protein 2 (DDB2). Here, we demonstrated that the ovarian CSC subpopulation can be maintained via cancer cell dedifferentiation, and DDB2 is able to suppress this non-CSC-to-CSC conversion by repression of ALDH1A1 transcription...
May 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29748386/frequent-irf1-binding-at-remote-elements-without-histone-modification
#18
Mohamed Abou El Hassan, Katherine Huang, Zhaodong Xu, Tao Yu, Rod Bremner
Transcriptional activators bind DNA and recruit cofactors to modify chromatin.  The extent to which these two events are separable is unclear.  Here, using a custom ChIP tiling array to map chromatin modifications, we show that Interferon-γ-induced DNA-binding of signal transducer and activator of transcription 1 (STAT1), typically associated with the transcription factor IFN regulatory factor 1 (IRF1), causes histone acetylation (H3ac, H4ac). In contrast, among IRF1 sites lacking concomitant STAT1 recruitment, only 25% underwent inducible histone acetylation, 31% exhibited constitutive histone acetylation, and 44% had no histone acetylation...
May 10, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29743723/dysregulation-of-ezh2-mir-138-axis-contributes-to-drug-resistance-in-multiple-myeloma-by-downregulating-rbpms
#19
Nasrin Rastgoo, Maryam Pourabdollah, Jahangir Abdi, Donna Reece, Hong Chang
EZH2 is highly expressed in multiple myeloma (MM). However, the molecular mechanisms underlying EZH2 overexpression and its role in drug resistance of MM remain undefined. Here we show that EZH2 is upregulated in drug-resistant MM cells and its aberrant overexpression is associated with poor prognosis of MM patients. Overexpression of EZH2 in parental MM cells renders them resistant to anti-myeloma drugs and suppression of EZH2 displays the opposite effects. Using miRNA target scan algorithms, we identify miR-138 as a regulator of EZH2, which is conversely repressed by EZH2-induced H3K27 trimethylation in MM-resistant cell lines and primary tumor cells...
April 24, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29743404/-epigenetic-aberrations-in-adult-t-cell-leukemia-lymphoma-and-development-of-a-novel-ezh1-2-inhibitor
#20
Makoto Yamagishi
Histone H3 lysine 27 tri-methylation (H3K27me3) -dependent transcription regulation is a fundamental process of gene control. Although EZH2 mutation is observed in certain lymphoma types, many other cancers show global H3K27me3 accumulation irrespective of mutation. However, the underlying mechanisms of gene silencing and therapeutic efficacies of epigenetic drugs remain unclear. In this study, we showed that globally-accumulated H3K27me3 is induced by both cis-bound EZH1 and EZH2 in mature lymphocyte-derived malignancies...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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