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Utx h3k27

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https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#1
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28970783/the-histone-h3k27-demethylase-utx-regulates-synaptic-plasticity-and-cognitive-behaviors-in-mice
#2
Gang-Bin Tang, Yu-Qiang Zeng, Pei-Pei Liu, Ting-Wei Mi, Shuang-Feng Zhang, Shang-Kun Dai, Qing-Yuan Tang, Lin Yang, Ya-Jie Xu, Hai-Liang Yan, Hong-Zhen Du, Zhao-Qian Teng, Feng-Quan Zhou, Chang-Mei Liu
Histone demethylase UTX mediates removal of repressive trimethylation of histone H3 lysine 27 (H3K27me3) to establish a mechanistic switch to activate large sets of genes. Mutation of Utx has recently been shown to be associated with Kabuki syndrome, a rare congenital anomaly syndrome with dementia. However, its biological function in the brain is largely unknown. Here, we observe that deletion of Utx results in increased anxiety-like behaviors and impaired spatial learning and memory in mice. Loss of Utx in the hippocampus leads to reduced long-term potentiation and amplitude of miniature excitatory postsynaptic current, aberrant dendrite development and defective synapse formation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28732206/a-utx-mll4-p300-transcriptional-regulatory-network-coordinately-shapes-active-enhancer-landscapes-for-eliciting-transcription
#3
Shu-Ping Wang, Zhanyun Tang, Chun-Wei Chen, Miho Shimada, Richard P Koche, Lan-Hsin Wang, Tomoyoshi Nakadai, Alan Chramiec, Andrei V Krivtsov, Scott A Armstrong, Robert G Roeder
Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1(+)/H3K27ac(+)) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28723656/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#4
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28669924/histone-h3-lysine-4-methyltransferase-kmt2d
#5
REVIEW
Eugene Froimchuk, Younghoon Jang, Kai Ge
Histone-lysine N-methyltransferase 2D (KMT2D), also known as MLL4 and MLL2 in humans and Mll4 in mice, belongs to a family of mammalian histone H3 lysine 4 (H3K4) methyltransferases. It is a large protein over 5500 amino acids in size and is partially functionally redundant with KMT2C. KMT2D is widely expressed in adult tissues and is essential for early embryonic development. The C-terminal SET domain is responsible for its H3K4 methyltransferase activity and is necessary for maintaining KMT2D protein stability in cells...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28534508/utx-promotes-hormonally-responsive-breast-carcinogenesis-through-feed-forward-transcription-regulation-with-estrogen-receptor
#6
G Xie, X Liu, Y Zhang, W Li, S Liu, Z Chen, B Xu, J Yang, L He, Z Zhang, T Jin, X Yi, L Sun, Y Shang, J Liang
UTX is implicated in embryonic development and lineage specification. However, how this X-linked histone demethylase contributes to the occurrence and progression of breast cancer remains to be clarified. Here we report that UTX is physically associated with estrogen receptor (ER) and functions in ER-regulated transcription. We showed that UTX coordinates with JHDM1D and CBP to direct H3K27 methylation-acetylation transition and to create a permissive chromatin state on ER targets. Genome-wide analysis of the transcriptional targets of UTX by ChIP-seq identified a set of genes such as chemokine receptor CXCR4 that are intimately involved in breast cancer tumorigenesis and metastasis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28529687/histone-demethylases-utx-and-jmjd3-are-required-for-nkt-cell-development-in-mice
#7
Daniel Northrup, Ryoji Yagi, Kairong Cui, William R Proctor, Chaochen Wang, Katarzyna Placek, Lance R Pohl, Rongfu Wang, Kai Ge, Jinfang Zhu, Keji Zhao
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#8
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28423010/correction-the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#9
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0173713.].
2017: PloS One
https://www.readbyqxmd.com/read/28402853/structure-of-nascent-chromatin-is-essential-for-hematopoietic-lineage-specification
#10
Svetlana Petruk, Samanta A Mariani, Marco De Dominici, Patrizia Porazzi, Valentina Minieri, Jingli Cai, Lorraine Iacovitti, Neal Flomenberg, Bruno Calabretta, Alexander Mazo
The role of chromatin structure in lineage commitment of multipotent hematopoietic progenitors (HPCs) is presently unclear. We show here that CD34(+) HPCs possess a post-replicative chromatin globally devoid of the repressive histone mark H3K27me3. This H3K27-unmodified chromatin is required for recruitment of lineage-determining transcription factors (TFs) C/EBPα, PU.1, and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or erythroid commitment. Blocking DNA replication or increasing H3K27me3 levels prevents recruitment of these TFs to DNA and suppresses cytokine-induced erythroid or myeloid differentiation...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28319137/the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#11
Kazushige Ota, Kit I Tong, Kouichiro Goto, Shuta Tomida, Akiyoshi Komuro, Zhong Wang, Kazuto Nishio, Hitoshi Okada
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28130569/histone-demethylase-utx-counteracts-glucocorticoid-deregulation-of-osteogenesis-by-modulating-histone-dependent-and-independent-pathways
#12
Feng-Sheng Wang, Wei-Shiung Lian, Mel S Lee, Wen-Tsan Weng, Ying-Hsien Huang, Yu-Shan Chen, Yi-Chih Sun, Shing-Long Wu, Pei-Chin Chuang, Jih-Yang Ko
Excess glucocorticoid administration impairs osteogenic activities, which raises the risk of osteoporotic disorders. Epigenetic methylation of DNA and histone regulates the lineage commitment of progenitor cells. This study was undertaken to delineate the actions of histone lysine demethylase 6a (UTX) with regard to the glucocorticoid impediment of osteogenic differentiation. Osteogenic progenitor cells responded to supraphysiological glucocorticoid by elevating CpG dinucleotide methylation proximal to transcription start sites within Runx2 and osterix promoters and Wnt inhibitor Dickkopf-1 (Dkk1) expression concomitant with low UTX expression...
May 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28027012/dynamic-chromatin-regulation-at-notch-target-genes
#13
Benedetto Daniele Giaimo, Franz Oswald, Tilman Borggrefe
RBPJ is the central transcription factor that controls the Notch-dependent transcriptional response by coordinating repressing histone H3K27 deacetylation and activating histone H3K4 methylation. Here, we discuss the molecular mechanisms how RBPJ interacts with opposing NCoR/HDAC-corepressing or KMT2D/UTX-coactivating complexes and how this is controlled by phosphorylation of chromatin modifiers.
January 2017: Transcription
https://www.readbyqxmd.com/read/27983522/different-expression-patterns-of-histone-h3k27-demethylases-in-renal-cell-carcinoma-and-bladder-cancer
#14
Zehui Hong, Hui Li, Lili Li, Weilong Wang, Ting Xu
OBJECTIVE: UTX and JMJD3 are recently identified histone H3 lysine 27 (H3K27) demethylases. Many studies have shown aberrant H3K27 trimethylation (H3K27me3) levels widely exist in multiple cancers, and that altered H3K27me3 levels are correlated with tumorigenesis and tumor progression. To investigate expression patterns of UTX and JMJD3 genes in renal cell carcinoma (RCC) and bladder cancer and the relationship between gene expression and tumor development. MATERIAL AND METHODS: Samples were collected from 35 patients with RCC and 21 patients with bladder cancer and qRT-PCR was performed...
2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/27671333/utx-1-regulates-tat-induced-hiv-1-transactivation-via-changing-the-methylated-status-of-histone-h3
#15
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
#16
REVIEW
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...
November 1, 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
#17
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
#18
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...
May 2017: 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
#19
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
#20
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...
June 28, 2016: Oncotarget
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