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https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#1
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28808080/characterization-of-the-human-thyroid-epigenome
#2
Celia Siu, Sam Michael Wiseman, Sitanshu Gakkhar, Alireza Heravi-Moussavi, Misha Bilenky, Annaick Carles, Thomas Sierocinski, Angela Tam, Eric Yang Zhao, Katayoon Kasaian, Richard A Moore, Andrew J Mungall, Blair Walker, Thomas Thomson, Marco A Marra, Martin Hirst, Steven Jones
The thyroid gland, necessary for normal human growth and development, functions as an essential regulator of metabolism by the production and secretion of appropriate levels of thyroid hormone. However, assessment of abnormal thyroid function may be challenging suggesting a more fundamental understanding of normal function is needed. One way to characterize normal gland function is to study the epigenome and resulting transcriptome within its constituent cells. This study generates the first published reference epigenomes for human thyroid from four individuals using ChIP-seq and RNA-seq...
August 14, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28807939/prc2-mediated-transcriptomic-alterations-at-the-embryonic-stage-govern-tumorigenesis-and-clinical-outcome-in-mycn-driven-neuroblastoma
#3
Shoma Tsubota, Satoshi Kishida, Teppei Shimamura, Miki Ohira, Satoshi Yamashita, Dongliang Cao, Shinichi Kiyonari, Toshikazu Ushijima, Kenji Kadomatsu
Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma. Using this method, we found that tumorigenic cells were evident as early as day E13.5 during embryo development, when the MYC and PRC2 transcriptomes were significantly altered...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28801683/regulation-of-tumour-related-genes-by-dynamic-epigenetic-alteration-at-enhancer-regions-in-gastric-epithelial-cells-infected-by-epstein-barr-virus
#4
Atsushi Okabe, Sayaka Funata, Keisuke Matsusaka, Hiroe Namba, Masaki Fukuyo, Bahityar Rahmutulla, Motohiko Oshima, Atsushi Iwama, Masashi Fukayama, Atsushi Kaneda
Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801151/correlation-between-desiccation-stress-response-and-epigenetic-modifications-of-genes-in-drosophila-melanogaster-an-example-of-environment-epigenome-interaction
#5
Vineeta Sharma, Surbhi Kohli, Vani Brahmachari
Animals from different phyla including arthropods tolerate water stress to different extent. This tolerance is accompanied by biochemical changes which in turn are due to transcriptional alteration. The changes in transcription can be an indirect effect on some of the genes, ensuing from the effect of stress on the regulators of transcription including epigenetic regulators. Within this paradigm, we investigated the correlation between stress response and epigenetic modification underlying gene expression modulation during desiccation stress in Canton-S...
August 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28793256/dynamics-of-rna-polymerase-ii-pausing-and-bivalent-histone-h3-methylation-during-neuronal-differentiation-in-brain-development
#6
Jiancheng Liu, Xiwei Wu, Heying Zhang, Gerd P Pfeifer, Qiang Lu
During cellular differentiation, genes important for differentiation are expected to be silent in stem/progenitor cells yet can be readily activated. RNA polymerase II (Pol II) pausing and bivalent chromatin marks are two paradigms suited for establishing such a poised state of gene expression; however, their specific contributions in development are not well understood. Here we characterized Pol II pausing and H3K4me3/H3K27me3 marks in neural progenitor cells (NPCs) and their daughter neurons purified from the developing mouse cortex...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28790329/kdm4b-mediated-reduction-of-h3k9me3-and-h3k36me3-levels-improves-somatic-cell-reprogramming-into-pluripotency
#7
Jingwei Wei, Jisha Antony, Fanli Meng, Paul MacLean, Rebekah Rhind, Götz Laible, Björn Oback
Correct reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3). Upon inducing Kdm4b, H3K9/36me3 levels significantly decreased compared to non-induced controls. Concurrently, H3K9me1 levels significantly increased, while H3K9me2 and H3K27me3 remained unchanged...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28783698/maintenance-of-macrophage-transcriptional-programs-and-intestinal-homeostasis-by-epigenetic-reader-sp140
#8
Stuti Mehta, D Alexander Cronkite, Megha Basavappa, Tahnee L Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A Morrison, Jose D Pagan, Robert M Anthony, Pierre Tonnerre, Georg M Lauer, James C Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J Xavier, Terry K Means, Kate L Jeffrey
Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28776579/significance-of-h3k27me3-loss-in-the-diagnosis-of-malignant-peripheral-nerve-sheath-tumors
#9
Melike Pekmezci, Areli K Cuevas-Ocampo, Arie Perry, Andrew E Horvai
The diagnosis of malignant peripheral nerve sheath tumors can be challenging and other spindle cell sarcomas commonly enter in the differential diagnosis. Loss of trimethylation at lysine 27 of histone-H3 (H3K27me3) by immunohistochemistry was recently described in malignant peripheral nerve sheath tumors. However, its specificity remains controversial. We therefore studied 82 synovial sarcomas, 39 malignant peripheral nerve sheath tumors, and 10 fibrosarcomatous dermatofibrosarcoma protuberans for H3K27me3 loss by immunohistochemistry...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28765163/epigenome-profiling-and-editing-of-neocortical-progenitor-cells-during-development
#10
Mareike Albert, Nereo Kalebic, Marta Florio, Naharajan Lakshmanaperumal, Christiane Haffner, Holger Brandl, Ian Henry, Wieland B Huttner
The generation of neocortical neurons from neural progenitor cells (NPCs) is primarily controlled by transcription factors binding to DNA in the context of chromatin. To understand the complex layer of regulation that orchestrates different NPC types from the same DNA sequence, epigenome maps with cell type resolution are required. Here, we present genomewide histone methylation maps for distinct neural cell populations in the developing mouse neocortex. Using different chromatin features, we identify potential novel regulators of cortical NPCs...
August 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28764817/the-rpmi-1640-vitamin-mixture-promotes-bovine-blastocyst-development-in-vitro-and-downregulates-gene-expression-of-txnip-with-epigenetic-modification-of-associated-histones
#11
S Ikeda, M Sugimoto, S Kume
Diverse environmental conditions surrounding preimplantation embryos, including available nutrients, affect their metabolism and development in both short- and long-term manner. Thioredoxin-interacting protein (TXNIP) is a possible marker for preimplantation stress that is implicated in in vitro fertilization- (IVF) induced long-term DOHaD effects. B vitamins, as participants in one-carbon metabolism, may affect preimplantation embryos by epigenetic alterations of metabolically and developmentally important genes...
August 2, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28762137/a-clinicopathologic-study-of-head-and-neck-malignant-peripheral-nerve-sheath-tumors
#12
Adepitan A Owosho, Cherry L Estilo, Joseph M Huryn, Ping Chi, Cristina R Antonescu
Head and neck high grade malignant peripheral nerve sheath tumors (HN-MPNSTs) are rare highly aggressive soft tissue sarcomas that show overlapping morphologic and immunophenotypic features with melanoma and other high grade sarcomas, resulting in diagnostic challenges, particularly in sporadic settings. Recent discoveries have implicated loss of function mutations in the polycomb repressive complex 2 (PRC2) components, including EED or SUZ12 genes, as one of the leading pathogenetic mechanisms in high grade MPNST...
July 31, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28759577/modular-function-of-long-noncoding-rna-coldair-in-the-vernalization-response
#13
Dong-Hwan Kim, Yanpeng Xi, Sibum Sung
The long noncoding RNA COLDAIR is necessary for the repression of a floral repressor FLOWERING LOCUS C (FLC) during vernalization in Arabidopsis thaliana. The repression of FLC is mediated by increased enrichment of Polycomb Repressive Complex 2 (PRC2) and subsequent trimethylation of Histone H3 Lysine 27 (H3K27me3) at FLC chromatin. In this study we found that the association of COLDAIR with chromatin occurs only at the FLC locus and that the central region of the COLDAIR transcript is critical for this interaction...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28758855/targeting-dna-hypermethylation-computational-modeling-of-dna-demethylation-treatment-of-acute-myeloid-leukemia
#14
Jens Przybilla, Lydia Hopp, Michael Lübbert, Markus Loeffler, Joerg Galle
In acute myeloid leukemia (AML) DNA hypermethylation of gene promoters is frequently observed and often correlates with a block of differentiation. Treatment of AML patients with DNA methyltransferase inhibitors results in global hypomethylation of genes and, thereby, can lead to a reactivation of the differentiation capability. Unfortunately, after termination of treatment both hypermethylation and differentiation block return in most cases. Here, we apply, for the first time, a computational model of epigenetic regulation of transcription in order to: i) provide a mechanistic understanding of the DNA (de-) methylation process in AML and; ii) improve DNA demethylation treatment strategies...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28755519/hierarchical-role-for-transcription-factors-and-chromatin-structure-in-genome-organization-along-adipogenesis
#15
Avital Sarusi Portuguez, Michal Schwartz, Rasmus Siersbaek, Ronni Nielsen, Myong-Hee Sung, Susanne Mandrup, Tommy Kaplan, Ofir Hakim
The three dimensional folding of mammalian genomes is cell-type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin associating factors, the mechanisms driving the co-localization of active chromosomal domains and the role of this organization in regulating the transcription program in adipocytes are not clear. Analysis of genome-wide chromosomal associations revealed cell type-specific spatial clustering of adipogenic genes in 3T3-L1 cells...
July 29, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28754985/epigenetic-changes-in-myelofibrosis-distinct-methylation-changes-in-the-myeloid-compartments-and-in-cases-with-asxl1-mutations
#16
Helene Myrtue Nielsen, Christen Lykkegaard Andersen, Maj Westman, Lasse Sommer Kristensen, Fazila Asmar, Torben Arvid Kruse, Mads Thomassen, Thomas Stauffer Larsen, Vibe Skov, Lise Lotte Hansen, Ole Weis Bjerrum, Hans Carl Hasselbalch, Vasu Punj, Kirsten Grønbæk
This is the first study to compare genome-wide DNA methylation profiles of sorted blood cells from myelofibrosis (MF) patients and healthy controls. We found that differentially methylated CpG sites located to genes involved in 'cancer' and 'embryonic development' in MF CD34+ cells, in 'inflammatory disease' in MF mononuclear cells, and in 'immunological diseases' in MF granulocytes. Only few differentially methylated CpG sites were common among the three cell populations. Mutations in the epigenetic regulators ASXL1 (47%) and TET2 (20%) were not associated with a specific DNA methylation pattern using an unsupervised approach...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753554/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#17
Sayaka Funata, Keisuke Matsusaka, Ryota Yamanaka, Shogo Yamamoto, Atsushi Okabe, Masaki Fukuyo, Hiroyuki Aburatani, Masashi Fukayama, Atsushi Kaneda
Aberrant DNA hypermethylation is a major epigenetic mechanism to inactivate tumor suppressor genes in cancer. Epstein-Barr virus positive gastric cancer is the most frequently hypermethylated tumor among human malignancies. Herein, we performed comprehensive analysis of epigenomic alteration during EBV infection, by Infinium HumanMethylation 450K BeadChip for DNA methylation and ChIP-sequencing for histone modification alteration during EBV infection into gastric cancer cell line MKN7. Among 7,775 genes with increased DNA methylation in promoter regions, roughly half were "DNA methylation-sensitive" genes, which acquired DNA methylation in the whole promoter regions and thus were repressed...
July 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28752843/loss-of-h3k27-trimethylation-is-not-suitable-for-distinguishing-malignant-peripheral-nerve-sheath-tumor-from-melanoma-a-study-of-387-cases-including-mimicking-lesions
#18
Sophie Le Guellec, Nicolas Macagno, Valérie Velasco, Laurence Lamant, Marick Lae, Thomas Filleron, Nausicaa Malissen, Elisabeth Cassagnau, Philippe Terrier, Christine Chevreau, Dominique Ranchere-Vince, Jean-Michel Coindre
The diagnosis of malignant peripheral nerve sheath tumor remains challenging, especially in the sporadic setting. Malignant peripheral nerve sheath tumor is a rare malignancy, and owing to the lack of specific histological criteria, immunohistochemical and molecular diagnostic markers, several differential diagnoses must be considered, in particular melanoma. Recently, inactivation of the polycomb repressive complex 2 (PRC2), induced by inactivating mutations in two of its critical constituents SUZ12 and EED, was reported in a large subset of malignant peripheral nerve sheath tumors...
July 28, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28748258/ezh2-is-involved-in-silencing-of-wnt5a-during-epithelial-mesenchymal-transition-of-colon-cancer-cell-line
#19
Jianxin Tao, Liping Shi, Longchang Huang, Haoze Shi, Hang Chen, Yixin Wang, Tong Wang
PURPOSE: Transforming growth factor-β (TGF-β) induction of epithelial-mesenchymal transition (EMT) in SW480 was established as a system for studies of colon cancer metastasis. However, the epigenetic mechanisms underlying this process remain unknown. In mammal, polycomb repressive complex-2 (PRC2) is a highly conserved histone methyltransferase involved in epigenetic regulations. Enhancer of zeste Homolog 2 (EZH2) is the catalytic subunit of PRC2, which catalyzes methylation of lysine 27 of histone H3 (H3K27)...
July 26, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28747748/the-epigenetic-landscape-of-promoter-genome-wide-analysis-in-breast-cancer
#20
Seher Karsli-Ceppioglu, Aslihan Dagdemir, Gaëlle Judes, André Lebert, Frédérique Penault-Llorca, Yves-Jean Bignon, Dominique Bernard-Gallon
Breast cancer is a heterogeneous disease due to its clinico-pathological features and response to therapy. The classification of breast tumors based on their hormone receptor status and pathologic features. Post-translational histone modifications come into prominence for regulation of gene expression in cancer pathogenesis. Here, we analyzed dysregulation of H3K9ac and H3K27me3-enriched subtype-specific genes using ChIP-on-chip assay in breast cancer tumors and matched normal tissue samples. Breast cancer tumors were classified according to St Gallen Consensus 2013...
July 26, 2017: Scientific Reports
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