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Utx h3k27

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https://www.readbyqxmd.com/read/27671333/utx-1-regulates-tat-induced-hiv-1-transactivation-via-changing-the-methylated-status-of-histone-h3
#1
Hong-Sheng Zhang, Guang-Yuan Du, Yang Liu, Zhong-Guo Zhang, Zhen Zhou, Hu Li, Ke-Qing Dai, Xiao-Ying Yu, Xiao-Meng Gou
Epigenetic modifications are thought to be important for gene expression changes during HIV-1 transcription and replication. The removal of histone H3 lysine27 (H3K27) trimethylation mark by UTX-1 is important for the robust induction of many specific genes during Tat-mediated HIV-1 transactvation. We found that UTX-1 enzymatic activity is needed for Tat to remove a repressive mark H3K27me3 in the HIV-1 long terminal repeat (LTR). UTX-1 converted the chromatin structure to a more transcriptionally active state by up-regulation of H3K4 methylation and down-regulation of H3K27 methylation on the specific regions of HIV-1 LTR...
September 23, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27638352/mll3-mll4-compass-family-on-epigenetic-regulation-of-enhancer-function-and-cancer
#2
Christie C Sze, Ali Shilatifard
During development, precise spatiotemporal patterns of gene expression are coordinately controlled by cis-regulatory modules known as enhancers. Their crucial role in development helped spur numerous studies aiming to elucidate the functional properties of enhancers within their physiological and disease contexts. In recent years, the role of enhancer malfunction in tissue-specific tumorigenesis is increasingly investigated. Here, we direct our focus to two primary players in enhancer regulation and their role in cancer pathogenesis: MLL3 and MLL4, members of the COMPASS family of histone H3 lysine 4 (H3K4) methyltransferases, and their complex-specific subunit UTX, a histone H3 lysine 27 (H3K27) demethylase...
September 16, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27578004/histone-h3k27-trimethylation-modulates-5-fluorouracil-resistance-by-inhibiting-pu-1-binding-to-the-dpyd-promoter
#3
Rentian Wu, Qian Nie, Erin E Tapper, Calvin R Jerde, Garrett S Dunlap, Shikshya Shrestha, Tarig A Elraiyah, Steven M Offer, Robert B Diasio
The antimetabolite 5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs. Dihydropyrimidine dehydrogenase (DPD) is a major determinant of 5-FU response and toxicity. Although DPYD variants may affect 5-FU metabolism, they do not completely explain the reported variability in DPD function or the resultant differences in treatment response. Here, we report that H3K27 trimethylation (H3K27me3) at the DPYD promoter regulated by Ezh2 and UTX suppresses DPYD expression by inhibiting transcription factor PU...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27367247/increased-expression-of-the-histone-h3-lysine-4-methyltransferase-mll4-and-the-histone-h3-lysine-27-demethylase-utx-prolonging-the-overall-survival-of-patients-with-glioblastoma-and-a-methylated-mgmt-promoter
#4
Jinho Kim, Sung-Hun Lee, Ji Hwan Jang, Mee-Seon Kim, Eun Hee Lee, Young Zoon Kim
OBJECTIVE The purpose of the present study was to investigate the epigenetic and prognostic roles of an H3K4 methyltransferase (mixed lineage leukemia 4 [MLL4]) and H3K27 demethylase (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome [UTX]) in progression-free survival (PFS) and overall survival (OS) of patients with glioblastoma (GBM) who were treated with radiotherapy, chemotherapy, or both after resection. In addition, the authors examined methylation at the promoter of the O-6-methylguanine-DNA methyltransferase (MGMT) gene and other prognostic factors predicting length of PFS and OS in these patients...
July 1, 2016: Journal of Neurosurgery
https://www.readbyqxmd.com/read/27228653/-product-of-the-bmi1-a-key-component-of-polycomb-positively-regulates-adipocyte-differentiation-of-mouse-mesenchymal-stem-cells
#5
N S Petrov, N A Vereschagina, E N Sushilova, A V Kropotov, N F Miheeva, B V Popov
Bmil is a key component of Polycomb (PcG), which in mammals controls the basic functions of mammalian somatic stem cells (SSC) such as self-renewal and differentiation. Bmi1 supports SSC via transcriptional suppression of genes associated with cell cycle and differentiation. The most studied target genes of Bmi1 are the genes of Ink4 locus, CdkI p16(Ink4a) and p1(Arf), suppression of which due to activating mutations of the BMI1 results in formation of cancer stem cells (CSC) and carcinomas in various tissues...
2016: Tsitologiia
https://www.readbyqxmd.com/read/27224921/screen-identified-selective-inhibitor-of-lysine-demethylase-5a-blocks-cancer-cell-growth-and-drug-resistance
#6
Molly Gale, Joyce Sayegh, Jian Cao, Michael Norcia, Peter Gareiss, Denton Hoyer, Jane S Merkel, Qin Yan
Lysine demethylase 5A (KDM5A/RBP2/JARID1A) is a histone lysine demethylase that is overexpressed in several human cancers including lung, gastric, breast and liver cancers. It plays key roles in important cancer processes including tumorigenesis, metastasis, and drug tolerance, making it a potential cancer therapeutic target. Chemical tools to analyze KDM5A demethylase activity are extremely limited as available inhibitors are not specific for KDM5A. Here, we characterized KDM5A using a homogeneous luminescence-based assay and conducted a screen of about 9,000 small molecules for inhibitors...
May 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27132888/mechanism-and-role-of-sox2-repression-in-seminoma-relevance-to-human-germline-specification
#7
Ritu Kushwaha, Nirmala Jagadish, Manjunath Kustagi, Geetu Mendiratta, Marco Seandel, Rekha Soni, James E Korkola, Venkata Thodima, Andrea Califano, George J Bosl, R S K Chaganti
Human male germ cell tumors (GCTs) are derived from primordial germ cells (PGCs). The master pluripotency regulator and neuroectodermal lineage effector transcription factor SOX2 is repressed in PGCs and the seminoma (SEM) subset of GCTs. The mechanism of SOX2 repression and its significance to GC and GCT development currently are not understood. Here, we show that SOX2 repression in SEM-derived TCam-2 cells is mediated by the Polycomb repressive complex (PcG) and the repressive H3K27me3 chromatin mark that are enriched at its promoter...
May 10, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27106782/prognostic-value-of-utx-expression-in-patients-with-clear-cell-renal-cell-carcinoma
#8
Jiajun Wang, Li Liu, Wei Xi, Qilai Long, Yiwei Wang, Qi Bai, Yu Xia, Jiejie Xu, Jianming Guo
PURPOSE: Our previous studies have identified an abnormal H3K27 methylation status in clear cell renal cell carcinoma (ccRCC). Ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) has been demonstrated as a histone demethylase that specifically targets di-methyl groups and tri-methyl groups on lysine 27 of histone H3 (H3K27me2/3). Herein, we explored the prognostic value of tumoral UTX expression in patient with ccRCC. PATIENTS AND METHODS: We retrospectively enrolled 290 ccRCC patients underwent nephrectomy at a single institution between 2005 and 2007...
August 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27039394/epigenetic-dysfunction-in-turner-syndrome-immune-cells
#9
REVIEW
Bradly J Thrasher, Lee Kyung Hong, Jason K Whitmire, Maureen A Su
Turner syndrome (TS) is a chromosomal condition associated with partial or complete absence of the X chromosome that involves characteristic findings in multiple organ systems. In addition to well-known clinical characteristics such as short stature and gonadal failure, TS is also associated with T cell immune alterations and chronic otitis media, suggestive of a possible immune deficiency. Recently, ubiquitously transcribed tetratricopeptide repeat on the X chromosome (UTX), a histone H3 lysine 27 (H3K27) demethylase, has been identified as a downregulated gene in TS immune cells...
May 2016: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/26999603/utx-demethylase-activity-is-required-for-satellite-cell-mediated-muscle-regeneration
#10
Hervé Faralli, Chaochen Wang, Kiran Nakka, Aissa Benyoucef, Soji Sebastian, Lenan Zhuang, Alphonse Chu, Carmen G Palii, Chengyu Liu, Brendan Camellato, Marjorie Brand, Kai Ge, F Jeffrey Dilworth
The X chromosome-encoded histone demethylase UTX (also known as KDM6A) mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish transcriptionally permissive chromatin. Loss of UTX in female mice is embryonic lethal. Unexpectedly, male UTX-null mice escape embryonic lethality due to expression of UTY, a paralog that lacks H3K27 demethylase activity, suggesting an enzyme-independent role for UTX in development and thereby challenging the need for active H3K27 demethylation in vivo...
April 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/26986003/epigenetic-regulation-by-baf-mswi-snf-chromatin-remodeling-complexes-is-indispensable-for-embryonic-development
#11
Huong Nguyen, Godwin Sokpor, Linh Pham, Joachim Rosenbusch, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
The multi-subunit chromatin-remodeling SWI/SNF (known as BAF for Brg/Brm-associated factor) complexes play essential roles in development. Studies have shown that the loss of individual BAF subunits often affects local chromatin structure and specific transcriptional programs. However, we do not fully understand how BAF complexes function in development because no animal mutant had been engineered to lack entire multi-subunit BAF complexes. Importantly, we recently reported that double conditional knock-out (dcKO) of the BAF155 and BAF170 core subunits in mice abolished the presence of the other BAF subunits in the developing cortex...
May 18, 2016: Cell Cycle
https://www.readbyqxmd.com/read/26944678/utx-inhibition-as-selective-epigenetic-therapy-against-tal1-driven-t-cell-acute-lymphoblastic-leukemia
#12
Aissa Benyoucef, Carmen G Palii, Chaochen Wang, Christopher J Porter, Alphonse Chu, Fengtao Dai, Véronique Tremblay, Patricia Rakopoulos, Kulwant Singh, Suming Huang, Francoise Pflumio, Josée Hébert, Jean-Francois Couture, Theodore J Perkins, Kai Ge, F Jeffrey Dilworth, Marjorie Brand
T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of hematological tumors composed of distinct subtypes that vary in their genetic abnormalities, gene expression signatures, and prognoses. However, it remains unclear whether T-ALL subtypes differ at the functional level, and, as such, T-ALL treatments are uniformly applied across subtypes, leading to variable responses between patients. Here we reveal the existence of a subtype-specific epigenetic vulnerability in T-ALL by which a particular subgroup of T-ALL characterized by expression of the oncogenic transcription factor TAL1 is uniquely sensitive to variations in the dosage and activity of the histone 3 Lys27 (H3K27) demethylase UTX/KDM6A...
March 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/26819089/epigenetic-regulation-of-e-cadherin-expression-by-the-histone-demethylase-utx-in-colon-cancer-cells
#13
Lin Zha, Qiang Cao, Xin Cui, Fenfen Li, Houjie Liang, Bingzhong Xue, Hang Shi
Decreased epithelial cadherin (E-cadherin) gene expression, a hallmark of epithelial-mesenchymal transition (EMT), is essential for triggering metastatic advantage of the colon cancer. Genetic mechanisms underlying the regulation of E-cadherin expression in EMT have been extensively investigated; however, much is unknown about the epigenetic mechanism underlying this process. Here, we identified ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase involved in demethylating di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), as a positive regulator for the expression of E-cadherin in the colon cancer cell line HCT-116...
March 2016: Medical Oncology
https://www.readbyqxmd.com/read/26776360/design-and-discovery-of-new-pyrimidine-coupled-nitrogen-aromatic-rings-as-chelating-groups-of-jmjd3-inhibitors
#14
Jianping Hu, Xin Wang, Lin Chen, Min Huang, Wei Tang, Jianping Zuo, Yu-Chih Liu, Zhe Shi, Rongfeng Liu, Jingkang Shen, Bing Xiong
The histone methylation on lysine residues is one of the most studied post-translational modifications, and its aberrant states have been associated with many human diseases. In 2012, Kruidenier et al. reported GSK-J1 as a selective Jumonji H3K27 demethylase (JMJD3 and UTX) inhibitor. However, there is limited information on the structure-activity relationship of this series of compounds. Moreover, there are few scaffolds reported as chelating groups for Fe(II) ion in Jumonji demethylase inhibitors development...
February 1, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/26773213/resetting-the-epigenome-for-heart-regeneration
#15
REVIEW
Gregory A Quaife-Ryan, Choon Boon Sim, Enzo R Porrello, James E Hudson
In contrast to adults, recent evidence suggests that neonatal mice are able to regenerate following cardiac injury. This regenerative capacity is reliant on robust induction of cardiomyocyte proliferation, which is required for faithful regeneration of the heart following injury. However, cardiac regenerative potential is lost as cardiomyocytes mature and permanently withdraw from the cell cycle shortly after birth. Recently, a handful of factors responsible for the regenerative disparity between the adult and neonatal heart have been identified, but the proliferative response of adult cardiomyocytes following modulation of these factors rarely reaches neonatal levels...
October 2016: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/26762983/an-essential-role-for-utx-in-resolution-and-activation-of-bivalent-promoters
#16
Shilpa S Dhar, Sung-Hun Lee, Kaifu Chen, Guangjing Zhu, WonKyung Oh, Kendra Allton, Ohad Gafni, Young Zoon Kim, Alin S Tomoiga, Michelle Craig Barton, Jacob H Hanna, Zhibin Wang, Wei Li, Min Gyu Lee
Trimethylated histone H3 lysine 27 (H3K27me3) is linked to gene silencing, whereas H3K4me3 is associated with gene activation. These two marks frequently co-occupy gene promoters, forming bivalent domains. Bivalency signifies repressed but activatable states of gene expression and can be resolved to active, H3K4me3-prevalent states during multiple cellular processes, including differentiation, development and epithelial mesenchymal transition. However, the molecular mechanism underlying bivalency resolution remains largely unknown...
May 5, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/26733201/histone-deacetylase-1-hdac1-negatively-regulates-thermogenic-program-in-brown-adipocytes-via-coordinated-regulation-of-histone-h3-lysine-27-h3k27-deacetylation-and-methylation
#17
Fenfen Li, Rui Wu, Xin Cui, Lin Zha, Liqing Yu, Hang Shi, Bingzhong Xue
Inhibiting class I histone deacetylases (HDACs) increases energy expenditure, reduces adiposity, and improves insulin sensitivity in obese mice. However, the precise mechanism is poorly understood. Here, we demonstrate that HDAC1 is a negative regulator of the brown adipocyte thermogenic program. The Hdac1 level is lower in mouse brown fat (BAT) than white fat, is suppressed in mouse BAT during cold exposure or β3-adrenergic stimulation, and is down-regulated during brown adipocyte differentiation. Remarkably, overexpressing Hdac1 profoundly blocks, whereas deleting Hdac1 significantly enhances, β-adrenergic activation-induced BAT-specific gene expression in brown adipocytes...
February 26, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26655900/loss-of-baf-mswi-snf-complexes-causes-global-transcriptional-and-chromatin-state-changes-in-forebrain-development
#18
Ramanathan Narayanan, Mehdi Pirouz, Cemil Kerimoglu, Linh Pham, Robin J Wagener, Kamila A Kiszka, Joachim Rosenbusch, Rho H Seong, Michael Kessel, Andre Fischer, Anastassia Stoykova, Jochen F Staiger, Tran Tuoc
BAF (Brg/Brm-associated factors) complexes play important roles in development and are linked to chromatin plasticity at selected genomic loci. Nevertheless, a full understanding of their role in development and chromatin remodeling has been hindered by the absence of mutants completely lacking BAF complexes. Here, we report that the loss of BAF155/BAF170 in double-conditional knockout (dcKO) mice eliminates all known BAF subunits, resulting in an overall reduction in active chromatin marks (H3K9Ac), a global increase in repressive marks (H3K27me2/3), and downregulation of gene expression...
December 1, 2015: Cell Reports
https://www.readbyqxmd.com/read/26427469/regulation-of-retinal-development-via-the-epigenetic-modification-of-histone-h3
#19
Sumiko Watanabe, Akira Murakami
We are interested in the roles of epigenetic mechanisms in retinal development. By ChIP-qPCR using whole retinal extracts at various developmental stages, we found that the levels of methylation of histones H3K27 and H3K4 and acetylation of histone H3 at specific loci in various genes, which play critical roles in retinal proliferation and differentiation, changed dramatically during retinal development. We next focused on the roles of H3K27 trimethylation in retinal development. Ezh1 and Ezh2 are methyltransferases that act on H3K27, while Jmjd3 and Utx are demethylases...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/26306033/the-histone-demethylase-utx-promotes-brown-adipocyte-thermogenic-program-via-coordinated-regulation-of-h3k27-demethylation-and-acetylation
#20
Lin Zha, Fenfen Li, Rui Wu, Liana Artinian, Vincent Rehder, Liqing Yu, Houjie Liang, Bingzhong Xue, Hang Shi
Brown adipocytes function to dissipate energy as heat through adaptive thermogenesis. Understanding the molecular mechanisms underlying the brown fat thermogenic program may provide insights for the development of therapeutic approaches in the treatment of obesity. Most studies investigating the mechanisms underlying brown fat development focus on genetic mechanisms; little is known about the epigenetic mechanisms in this process. We have discovered that ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase for di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), plays a potential role in regulating brown adipocyte thermogenic program...
October 9, 2015: Journal of Biological Chemistry
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