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H3K27me3

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https://www.readbyqxmd.com/read/27926872/deletion-of-the-polycomb-group-protein-ezh2-leads-to-compromised-self-renewal-and-differentiation-defects-in-human-embryonic-stem-cells
#1
Adam Collinson, Amanda J Collier, Natasha P Morgan, Arnold R Sienerth, Tamir Chandra, Simon Andrews, Peter J Rugg-Gunn
Through the histone methyltransferase EZH2, the Polycomb complex PRC2 mediates H3K27me3 and is associated with transcriptional repression. PRC2 regulates cell-fate decisions in model organisms; however, its role in regulating cell differentiation during human embryogenesis is unknown. Here, we report the characterization of EZH2-deficient human embryonic stem cells (hESCs). H3K27me3 was lost upon EZH2 deletion, identifying an essential requirement for EZH2 in methylating H3K27 in hESCs, in contrast to its non-essential role in mouse ESCs...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926813/perturbation-of-h3k27me3-associated-epigenetic-processes-increases-agrobacterium-mediated-transformation
#2
Hidekazu Iwakawa, Benjamin C Carter, Brett C Bishop, Joe Ogas, Stanton B Gelvin
Agrobacterium-mediated transformation is a core technology for basic plant science and agricultural biotechnology. Improving transformation frequency is a major goal for plant transgenesis. We previously showed that T-DNA insertions in some histone genes decreased transformation susceptibility, whereas overexpression of several Arabidopsis H2A and H4 isoforms increased transformation. Overexpression of several histone H2B and H3 isoforms had little effect on transformation frequency. However, overexpression of histone H3-11 (HTR11) enhanced transformation...
December 7, 2016: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/27926531/an-annotated-list-of-bivalent-chromatin-regions-in-human-es-cells-a-new-tool-for-cancer-epigenetic-research
#3
Franck Court, Philippe Arnaud
CpG islands (CGI) marked by bivalent chromatin in stem cells are believed to be more prone to aberrant DNA methylation in tumor cells. The robustness and genome-wide extent of this instructive program in different cancer types remain to be determined. To address this issue we developed a user-friendly approach to integrate the stem cell chromatin signature in customized DNA methylation analyses. We used publicly available ChIP-sequencing datasets of several human embryonic stem cell (hESC) lines to determine the extent of bivalent chromatin genome-wide...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926488/blocking-ezh2-methylation-transferase-activity-by-gsk126-decreases-stem-cell-like-myeloma-cells
#4
Delong Zeng, Maoxing Liu, Jingxuan Pan
EZH2 is a critical epigenetic regulator that is deregulated in various types of cancers including multiple myeloma (MM). In the present study, we hypothesized that targeting EZH2 might induce apoptosis in myeloma cells including stem cell-like cells (CSCs). We investigated the effect of EZH2 inhibition on MM cells using a potent inhibitor (GSK126). The results showed that GSK126 effectively abrogated the methylated histone 3 (H3K27me3) level in MM.1S and LP1 cells, and inhibited the number of live cells and colony formation in soft agar of six MM cell lines...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27923998/interplay-between-h1-and-hmgn-epigenetically-regulates-olig1-2-expression-and-oligodendrocyte-differentiation
#5
Tao Deng, Yuri Postnikov, Shaofei Zhang, Lillian Garrett, Lore Becker, Ildikó Rácz, Sabine M Hölter, Wolfgang Wurst, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Michael Bustin
An interplay between the nucleosome binding proteins H1 and HMGN is known to affect chromatin dynamics, but the biological significance of this interplay is still not clear. We find that during embryonic stem cell differentiation loss of HMGNs leads to down regulation of genes involved in neural differentiation, and that the transcription factor OLIG2 is a central node in the affected pathway. Loss of HMGNs affects the expression of OLIG2 as well as that of OLIG1, two transcription factors that are crucial for oligodendrocyte lineage specification and nerve myelination...
December 6, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923061/comparative-transcriptomic-and-epigenomic-analyses-reveal-new-regulators-of-murine-brown-adipogenesis
#6
Reinhard Brunmeir, Jingyi Wu, Xu Peng, Sun-Yee Kim, Sofi G Julien, Qiongyi Zhang, Wei Xie, Feng Xu
Increasing energy expenditure through brown adipocyte recruitment is a promising approach to combat obesity. We report here the comprehensive profiling of the epigenome and transcriptome throughout the lineage commitment and differentiation of C3H10T1/2 mesenchymal stem cell line into brown adipocytes. Through direct comparison to datasets from differentiating white adipocytes, we systematically identify stage- and lineage-specific coding genes, lncRNAs and microRNAs. Utilizing chromatin state maps, we also define stage- and lineage-specific enhancers, including super-enhancers, and their associated transcription factor binding motifs and genes...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27918982/traffic-derived-particulate-matter-exposure-and-histone-h3-modification-a-repeated-measures-study
#7
Yinan Zheng, Marco Sanchez-Guerra, Zhou Zhang, Brian T Joyce, Jia Zhong, Jacob K Kresovich, Lei Liu, Wei Zhang, Tao Gao, Dou Chang, Citlalli Osorio-Yanez, Juan Jose Carmona, Sheng Wang, John P McCracken, Xiao Zhang, Yana Chervona, Anaite Díaz, Pier A Bertazzi, Petros Koutrakis, Choong-Min Kang, Joel Schwartz, Andrea A Baccarelli, Lifang Hou
BACKGROUND: Airborne particulate matter (PM) may induce epigenetic changes that potentially lead to chronic diseases. Histone modifications regulate gene expression by influencing chromatin structure that can change gene expression status. We evaluated whether traffic-derived PM exposure is associated with four types of environmentally inducible global histone H3 modifications. METHODS: The Beijing Truck Driver Air Pollution Study included 60 truck drivers and 60 office workers examined twice, 1-2 weeks apart, for ambient PM10 (both day-of and 14-day average exposures), personal PM2...
December 2, 2016: Environmental Research
https://www.readbyqxmd.com/read/27903964/lncrna-h19-inhibits-autophagy-by-epigenetically-silencing-of-diras3-in-diabetic-cardiomyopathy
#8
Chuanjun Zhuo, Ronghuan Jiang, Xiaodong Lin, Mingjing Shao
We previously generated a rat model of diabetic cardiomyopathy and found that the expression of long non-coding RNA H19 was downregulated. The present study was aimed to explore the pathogenic role of H19 in the development of diabetic cardiomyopathy. Overexpression of H19 in diabetic rats attenuated cardiomyocyte autophagy and improved left ventricular function. High glucose was found to reduce H19 expression and increase autophagy in cultured neonatal cardiomyocytes. The results of RNA-binding protein immunoprecipitation showed that H19 could directly bind with EZH2 in cardiomyocytes...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27903907/chromatin-binding-of-gcn5-in-drosophila-is-largely-mediated-by-cp190
#9
Tamer Ali, Marcus Krüger, Sabin Bhuju, Michael Jarek, Marek Bartkuhn, Rainer Renkawitz
Centrosomal 190 kDa protein (CP190) is a promoter binding factor, mediates long-range interactions in the context of enhancer-promoter contacts and in chromosomal domain formation. All Drosophila insulator proteins bind CP190 suggesting a crucial role in insulator function. CP190 has major effects on chromatin, such as depletion of nucleosomes, high nucleosomal turnover and prevention of heterochromatin expansion. Here, we searched for enzymes, which might be involved in CP190 mediated chromatin changes. Eighty percent of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding...
November 29, 2016: Nucleic Acids Research
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
#10
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/27902686/genomic-characterization-of-metformin-hepatic-response
#11
Marcelo R Luizon, Walter L Eckalbar, Yao Wang, Stacy L Jones, Robin P Smith, Megan Laurance, Lawrence Lin, Paul J Gallins, Amy S Etheridge, Fred Wright, Yihui Zhou, Cliona Molony, Federico Innocenti, Sook Wah Yee, Kathleen M Giacomini, Nadav Ahituv
Metformin is used as a first-line therapy for type 2 diabetes (T2D) and prescribed for numerous other diseases. However, its mechanism of action in the liver has yet to be characterized in a systematic manner. To comprehensively identify genes and regulatory elements associated with metformin treatment, we carried out RNA-seq and ChIP-seq (H3K27ac, H3K27me3) on primary human hepatocytes from the same donor treated with vehicle control, metformin or metformin and compound C, an AMP-activated protein kinase (AMPK) inhibitor (allowing to identify AMPK-independent pathways)...
November 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27895308/epigenetic-inhibition-of-mir-663b-by-long-non-coding-rna-hotair-promotes-pancreatic-cancer-cell-proliferation-via-up-regulation-of-insulin-like-growth-factor-2
#12
Huihua Cai, Yong An, Xuemin Chen, Donglin Sun, Tongbing Chen, Yan Peng, Feng Zhu, Yong Jiang, Xiaozhou He
Pancreatic cancer is one of the most deadly cancers with a poor prognosis. Although microRNAs are involving in the carcinogenesis and development of pancreatic cancer, little information is known regarding the role of miR-663b in pancreatic cancer. In this study, the expression of miR-663b in pancreatic cancer cells was down-regulated by hypermethylation in its putative promoter region, and overexpression of miR-663b repressed cell proliferation, invasion and migration, and induced apoptosis in pancreatic cancer cells...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893464/the-h3k9-dimethyltransferases-ehmt1-2-protect-against-pathological-cardiac-hypertrophy
#13
Bernard Thienpont, Jan Magnus Aronsen, Emma Louise Robinson, Hanneke Okkenhaug, Elena Loche, Arianna Ferrini, Patrick Brien, Kanar Alkass, Antonio Tomasso, Asmita Agrawal, Olaf Bergmann, Ivar Sjaastad, Wolf Reik, Hywel Llewelyn Roderick
Cardiac hypertrophic growth in response to pathological cues is associated with reexpression of fetal genes and decreased cardiac function and is often a precursor to heart failure. In contrast, physiologically induced hypertrophy is adaptive, resulting in improved cardiac function. The processes that selectively induce these hypertrophic states are poorly understood. Here, we have profiled 2 repressive epigenetic marks, H3K9me2 and H3K27me3, which are involved in stable cellular differentiation, specifically in cardiomyocytes from physiologically and pathologically hypertrophied rat hearts, and correlated these marks with their associated transcriptomes...
November 28, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27892467/jarid2-binds-mono-ubiquitylated-h2a-lysine-119-to-mediate-crosstalk-between-polycomb-complexes-prc1-and-prc2
#14
Sarah Cooper, Anne Grijzenhout, Elizabeth Underwood, Katia Ancelin, Tianyi Zhang, Tatyana B Nesterova, Burcu Anil-Kirmizitas, Andrew Bassett, Susanne M Kooistra, Karl Agger, Kristian Helin, Edith Heard, Neil Brockdorff
The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27889707/transgenerational-programming-of-longevity-through-e-z-mediated-histone-h3k27-trimethylation-in-drosophila
#15
Brian Xia, Ed Gerstin, Dustin E Schones, Wendong Huang, J Steven de Belle
Transgenerational effects on health and development of early-life nutrition have gained increased attention recently. However, the underlying mechanisms of transgenerational transmission are only starting to emerge, with epigenetics as perhaps the most important mechanism. We recently reported the first animal model to study transgenerational programming of longevity after early-life dietary manipulations, enabling investigations to identify underlying epigenetic mechanisms. We report here that post-eclosion dietary manipulation (PDM) with a low-protein (LP) diet upregulates the protein level of E(z), an H3K27 specific methyltransferase, leading to higher levels of H3K27 trimethylation (H3K27me3)...
November 25, 2016: Aging
https://www.readbyqxmd.com/read/27889452/an-rb-ezh2-complex-mediates-silencing-of-repetitive-dna-sequences
#16
Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch, Seth M Rubin, Mellissa R W Mann, Frederick A Dick
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments...
November 12, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27886392/deregulated-expression-of-ezh2-in-congenital-brainstem-disconnection
#17
P G Barth, E Aronica, S Fox, K Fluiter, M A J Weterman, A Poretti, D C Miller, E Boltshauser, B Harding, M Santi, F Baas
Congenital brainstem disconnection (CBSD) is an enigmatic embryo-fetal defect presenting as (sub)total absence of a segment between mesencephalon and lower brainstem. Rostro-caudal limits of the defect vary while the basal pons is always involved and the cerebellum is globally hypoplastic. A recent update and review[1] lists 14 cases, including 3 brain autopsy studies[1-3]. Necrosis and glial- or inflammatory reactions were absent. Inferior olivary nuclei were small or absent, pontine nuclei depleted, and the cerebellar dentate nuclei dysplastic...
November 25, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/27882937/ezh2-mediates-lidamycin-induced-cellular-senescence-through-regulating-p21-expression-in-human-colon-cancer-cells
#18
Ming-Quan Sha, Xiao-Li Zhao, Liang Li, Li-Hui Li, Yi Li, Tian-Geng Dong, Wei-Xin Niu, Li-Jun Jia, Rong-Guang Shao, Yong-Su Zhen, Zhen Wang
Lidamycin (LDM) is a novel member of the enediyne antibiotics identified in China with potent antitumor activity. However, it remains unclear whether LDM has potential molecular targets that may affect its antitumor activity. Enhancer of zeste homolog 2 (EZH2) functions as a histone lysine methyltransferase and mediates trimethylation on histone 3 lysine 27 (H3K27me3). High EZH2 level is found to be positively correlated with the aggressiveness, metastasis and poor prognosis of cancer. Here, we aim to study the role of EZH2 in LDM-induced senescence, as well as in the cytotoxicity of LDM in human colon cancer cells...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881822/lowered-h3k27me3-and-dna-hypomethylation-define-poorly-prognostic-pediatric-posterior-fossa-ependymomas
#19
Jill Bayliss, Piali Mukherjee, Chao Lu, Siddhant U Jain, Chan Chung, Daniel Martinez, Benjamin Sabari, Ashley S Margol, Pooja Panwalkar, Abhijit Parolia, Melike Pekmezci, Richard C McEachin, Marcin Cieslik, Benita Tamrazi, Benjamin A Garcia, Gaspare La Rocca, Mariarita Santi, Peter W Lewis, Cynthia Hawkins, Ari Melnick, C David Allis, Craig B Thompson, Arul M Chinnaiyan, Alexander R Judkins, Sriram Venneti
Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas...
November 23, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27879268/transcriptional-selectivity-of-epigenetic-therapy-in-cancer
#20
Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek, Jean-Pierre J Issa
A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343)...
November 22, 2016: Cancer Research
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