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H3K27me3

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https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#1
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28928895/mir-340-inhibits-triple-negative-breast-cancer-progression-by-reversing-ezh2-mediated-mirnas-dysregulated-expressions
#2
Zhendong Shi, Yang Li, Xiaomin Qian, Yunhui Hu, Jingjing Liu, Sheng Zhang, Jin Zhang
The anti-tumor efficacy of miR-340 has been recently characterized in cancers. However, the underlying mechanisms of miR-340 inhibited cell growth and invasion in triple-negative breast cancer (TNBC) have not been well elucidated. In this study, we found that miR-340 expression was negatively correlated with EZH2 (Enhancer of zeste homolog 2) expression in TNBC tissues and cell lines. Subsequent luciferase reporter assay confirmed that EZH2 was a novel molecule target of miR-340. Upregulated miR-340 levels by mimics transfection significantly inhibited the MDA-MB-231 and MDA-MB-468 breast cancer cells proliferation, invasion and migration, and induced more cell apoptosis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928876/heterochromatin-reduction-correlates-with-the-increase-of-the-kdm4b-and-kdm6a-demethylases-and-the-expression-of-pericentromeric-dna-during-the-acquisition-of-a-transformed-phenotype
#3
Cinthya Gurrion, Maritere Uriostegui, Mario Zurita
Cancer cells have alterations in chromatin organization, mostly a reduction in heterochromatin. How this process occurs during transformation and if it participates in the maintenance of a cancerous phenotype is not well understood. Here, using a transformation-inducible cell line, we analyzed the changes that occur in heterochromatin during transformation to a cancerous phenotype. After transformation, there is a reduction in heterochromatin bodies and a nuclear reorganization of HP1α. These occurrences correlate with reductions in H3K9me3 and H3K27me3 levels and with some of the enzymes that introduce these modifications...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28927461/additional-sex-combs-interacts-with-enhancer-of-zeste-and-trithorax-and-modulates-levels-of-trimethylation-on-histone-h3k4-and-h3k27-during-transcription-of-hsp70
#4
Taosui Li, Jacob W Hodgson, Svetlana Petruk, Alexander Mazo, Hugh W Brock
BACKGROUND: Maintenance of cell fate determination requires the Polycomb group for repression; the trithorax group for gene activation; and the enhancer of trithorax and Polycomb (ETP) group for both repression and activation. Additional sex combs (Asx) is a genetically identified ETP for the Hox loci, but the molecular basis of its dual function is unclear. RESULTS: We show that in vitro, Asx binds directly to the SET domains of the histone methyltransferases (HMT) enhancer of zeste [E(z)] (H3K27me3) and Trx (H3K4me3) through a bipartite interaction site separated by 846 amino acid residues...
September 19, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28925507/-epigallocatechin-3-gallate-and-ezh2-inhibitor-gsk343-have-similar-inhibitory-effects-and-mechanisms-of-action-on-colorectal-cancer-cells
#5
Le Ying, Feng Yan, Bryan R G Williams, Ping Xu, Xin Li, Yueling Zhao, Yiqun Hu, Yuefei Wang, Dakang Xu, Jing Dai
Epigallocatechin-3-gallate (EGCG) is a type of catechin. It exhibits excellent antioxidant effects and anti-tumor activities for cancer chemoprevention. The mechanism of anti-tumor effects of EGCG on different cancers has been studied for the past few decades, but remains controversial. To investigate the potential role that EGCG may play in the epigenetic regulation of colorectal cancer (CRC) cell line, we integrated bioinformatics analysis with experimental validation. We found that levels of the enhancer of zeste homolog 2 (EZH2) were significantly higher in CRC tissues compared to normal adjacent tissues, based on the Genomic Data Commons (GDC) data portal...
September 19, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28923964/repeat-e-anchors-xist-rna-to-the-inactive-x-chromosomal-compartment-through-cdkn1a-interacting-protein-ciz1
#6
Hongjae Sunwoo, David Colognori, John E Froberg, Yesu Jeon, Jeannie T Lee
X chromosome inactivation is an epigenetic dosage compensation mechanism in female mammals driven by the long noncoding RNA, Xist. Although recent genomic and proteomic approaches have provided a more global view of Xist's function, how Xist RNA localizes to the inactive X chromosome (Xi) and spreads in cis remains unclear. Here, we report that the CDKN1-interacting zinc finger protein CIZ1 is critical for localization of Xist RNA to the Xi chromosome territory. Stochastic optical reconstruction microscopy (STORM) shows a tight association of CIZ1 with Xist RNA at the single-molecule level...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923849/bivalent-epigenetic-control-of-oncofetal-gene-expression-in-cancer
#7
Sayyed K Zaidi, Seth E Frietze, Jonathan A Gordon, Jessica L Heath, Terri Messier, Deli Hong, Joseph R Boyd, Mingu Kang, Anthony N Imbalzano, Jane B Lian, Janet L Stein, Gary S Stein
Multiple mechanisms of epigenetic control that include DNA methylation, histone modification, non-coding RNAs, and mitotic gene bookmarking play pivotal roles in stringent gene regulation during lineage commitment and maintenance. Experimental evidence indicates that bivalent chromatin domains, i.e., regions of genome that are marked by both H3K4me3 (activating) and H3K27me3 (repressive) histone modifications, are a key property of pluripotent stem cells. Bivalency of developmental genes during the G1 phase of the pluripotent stem cell cycle contributes to cell fate decisions...
September 18, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28919981/regulation-of-cancer-epigenomes-with-a-histone-binding-synthetic-transcription-factor
#8
David B Nyer, Rene M Daer, Daniel Vargas, Caroline Hom, Karmella A Haynes
Chromatin proteins have expanded the mammalian synthetic biology toolbox by enabling control of active and silenced states at endogenous genes. Others have reported synthetic proteins that bind DNA and regulate genes by altering chromatin marks, such as histone modifications. Previously, we reported the first synthetic transcriptional activator, the "Polycomb-based transcription factor" (PcTF) that reads histone modifications through a protein-protein interaction between the polycomb chromodomain motif and trimethylated lysine 27 of histone H3 (H3K27me3)...
2017: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/28918030/lncrna-trerna1-function-as-an-enhancer-of-snai1-promotes-gastric-cancer-metastasis-by-regulating-epithelial-mesenchymal-transition
#9
Huazhang Wu, Ying Hu, Xiufang Liu, Wei Song, Pihai Gong, Kun Zhang, Zhenxing Chen, Menghan Zhou, Xiaohui Shen, Yanyan Qian, Hong Fan
Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (GC). TRERNA1 is significantly unregulated in GCs and GC cell lines. Increased TRERNA1 is positively correlated with lymph node metastasis of GCs. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays revealed that TRERNA1 functions as a scaffold to recruit EZH2 to epigenetically silence epithelial-mesenchymal transition marker CDH1 by H3K27me3 of its promoter region...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28912479/late-stage-differentiation-of-embryonic-pancreatic-%C3%AE-cells-requires-jarid2
#10
Sara Cervantes, Marta Fontcuberta-PiSunyer, Joan-Marc Servitja, Rebeca Fernandez-Ruiz, Ainhoa García, Lidia Sanchez, Young-Sook Lee, Ramon Gomis, Rosa Gasa
Jarid2 is a component of the Polycomb Repressor complex 2 (PRC2), which is responsible for genome-wide H3K27me3 deposition, in embryonic stem cells. However, Jarid2 has also been shown to exert pleiotropic PRC2-independent actions during embryogenesis. Here, we have investigated the role of Jarid2 during pancreas development. Conditional ablation of Jarid2 in pancreatic progenitors results in reduced endocrine cell area at birth due to impaired endocrine cell differentiation and reduced prenatal proliferation...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28911980/chromatin-organization-as-an-indicator-of-glucocorticoid-induced-natural-killer-cell-dysfunction
#11
Michael S Misale, Linda Witek Janusek, Dina Tell, Herbert L Mathews
It is well-established that psychological distress reduces natural killer cell immune function and that this reduction can be due to the stress-induced release of glucocorticoids. Glucocorticoids are known to alter epigenetic marks associated with immune effector loci, and are also known to influence chromatin organization. The purpose of this investigation was to assess the effect of glucocorticoids on natural killer cell chromatin organization and to determine the relationship of chromatin organization to natural killer cell effector function, e...
September 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#12
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28903418/histone-modification-alteration-coordinated-with-acquisition-of-promoter-dna-methylation-during-epstein-barr-virus-infection
#13
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...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900001/samd7-is-a-cell-type-specific-prc1-component-essential-for-establishing-retinal-rod-photoreceptor-identity
#14
Yoshihiro Omori, Shun Kubo, Tetsuo Kon, Mayu Furuhashi, Hirotaka Narita, Taro Kominami, Akiko Ueno, Ryotaro Tsutsumi, Taro Chaya, Haruka Yamamoto, Isao Suetake, Shinji Ueno, Haruhiko Koseki, Atsushi Nakagawa, Takahisa Furukawa
Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28898989/role-of-histone-h3k27-trimethylation-loss-as-a-marker-for-malignant-peripheral-nerve-sheath-tumor-in-fine-needle-aspiration-and-small-biopsy-specimens
#15
Jeffrey K Mito, Xiaohua Qian, Leona A Doyle, Jason L Hornick, Vickie Y Jo
Objectives: Accurate diagnosis of malignant peripheral nerve sheath tumor (MPNST) is often challenging on fine-needle aspiration (FNA) or core needle biopsy. Recurrent mutations in EED and SUZ12, which encode subunits of polycomb repressive complex 2 (PRC2), have been identified in 70% to 92% of MPNSTs; PRC2 inactivation leads to loss of trimethylation of lysine 27 of histone H3 (H3K27me3). We evaluated the utility of H3K27me3 immunohistochemistry for distinguishing MPNST from its cytomorphologic mimics...
August 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28887218/the-histone-lysine-methyltransferase-ezh2-is-required-for-maintenance-of-the-intestine-integrity-and-for-caudal-fin-regeneration-in-zebrafish
#16
Barbara Dupret, Pamela Völkel, Constance Vennin, Robert-Alain Toillon, Xuefen Le Bourhis, Pierre-Olivier Angrand
The histone lysine methyltransferase EZH2, as part of the Polycomb Repressive Complex 2 (PRC2), mediates H3K27me3 methylation which is involved in gene expression program repression. Through its action, EZH2 controls cell-fate decisions during the development and the differentiation processes. Here, we report the generation and the characterization of an ezh2-deficient zebrafish line. In contrast to its essential role in mouse early development, loss of ezh2 function does not affect zebrafish gastrulation. Ezh2 zebrafish mutants present a normal body plan but die at around 12 dpf with defects in the intestine wall, due to enhanced cell death...
September 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28880717/bivalent-histone-codes-on-wnt5a-during-odontogenic-differentiation
#17
Y Zhou, L Zheng, F Li, M Wan, Y Fan, X Zhou, W Du, C Pi, D Cui, B Zhang, J Sun, X Zhou
Lineage-committed differentiation is an essential biological program during odontogenesis, which is tightly regulated by lineage-specific genes. Some of these genes are modified by colocalization of H3K4me3 and H3K27me3 marks at promoter regions in progenitors. These modifications, named "bivalent domains," maintain genes in a poised state and then resolve for later activation or repression during differentiation. Wnt5a has been reported to promote odontogenic differentiation in dental mesenchyme. However, relatively little is known about the epigenetic modulations on Wnt5a activation during tooth development...
September 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28878842/efficacy-of-ezh2-inhibitory-drugs-in-human-papillomavirus-positive-and-human-papillomavirus-negative-oropharyngeal-squamous-cell-carcinomas
#18
Cameron D Lindsay, Morris A Kostiuk, Jeff Harris, Daniel A O'Connell, Hadi Seikaly, Vincent L Biron
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with rates of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) dramatically increasing. The overexpression of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for the trimethylation at lysine 27 of histone 3 (H3K27me3), is associated with a poor clinical prognosis and aggressive HPV-positive phenotypes. METHODS: We utilized three EZH2 pathway inhibitors, GSK-343, DZNeP, and EPZ-5687, and tested their efficacy in two HPV-positive and two HPV-negative OPSCC cell lines...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28876532/successful-treatment-with-doxorubicin-and-ifosfamide-for-mediastinal-malignant-peripheral-nerve-sheath-tumor-with-loss-of-h3k27me3-expression
#19
Noriko Seno, Toshirou Fukushima, Daisuke Gomi, Takashi Kobayashi, Nodoka Sekiguchi, Hidehiro Matsushita, Takesumi Ozawa, Yoshiko Tsukahara, Keiko Mamiya, Tomonobu Koizumi, Kenji Sano
Malignant peripheral nerve sheath tumor (MPNST) in the thorax is an extremely rare disease, and half of all cases of MPNST are associated with neurofibromatosis type I. Sporadic intrathoracic MPNST is difficult to diagnose and treat. Because of the rarity of intrathoracic MPNST, the optimal method of diagnosis and the efficacy of chemotherapy are unknown. Herein, we present a case of inoperable mediastinal MPNST, in which the diagnosis was immunohistochemically made by the loss of H3K27me3 expression in a transbronchial needle biopsy specimen...
September 6, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28874566/cellular-responses-to-human-cytomegalovirus-infection-induction-of-a-mesenchymal-to-epithelial-transition-met-phenotype
#20
Adam Oberstein, Thomas Shenk
Human cytomegalovirus (HCMV) is the prototypical human β-herpes virus. Here we perform a systems analysis of the HCMV host-cell transcriptome, using gene set enrichment analysis (GSEA) as an engine to globally map the host-pathogen interaction across two cell types. Our analysis identified several previously unknown signatures of infection, such as induction of potassium channels and amino acid transporters, derepression of genes marked with histone H3 lysine 27 trimethylation (H3K27me3), and inhibition of genes related to epithelial-to-mesenchymal transition (EMT)...
September 5, 2017: Proceedings of the National Academy of Sciences of the United States of America
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