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histone ubiquitination

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https://www.readbyqxmd.com/read/28314773/glucocorticoid-receptor-signaling-represses-the-antioxidant-response-by-inhibiting-histone-acetylation-mediated-by-the-transcriptional-activator-nrf2
#1
Md Morshedul Alam, Keito Okazaki, Linh Thi Thao Nguyen, Nao Ota, Hiroshi Kitamura, Shohei Murakami, Hiroki Shima, Kazuhiko Igarashi, Hiroki Sekine, Hozumi Motohashi
NRF2 (nuclear factor erythroid 2-related factor 2) is a key transcriptional activator that mediates the inducible expression of antioxidant genes. NRF2 is normally ubiquitinated by KEAP1 (Kelch-like ECH-associated protein 1) and subsequently degraded by proteasomes. Inactivation of KEAP1 by oxidative stress or electrophilic chemicals allows NRF2 to activate transcription through binding to antioxidant response elements (AREs) and recruiting histone acetyltransferase CBP (CREB-binding protein). While KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting other intracellular signaling cascades may impact NRF2 function...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28304275/pcgf6-prc1-suppresses-premature-differentiation-of-mouse-embryonic-stem-cells-by-regulating-germ-cell-related-genes
#2
Mitsuhiro Endoh, Takaho A Endo, Jun Shinga, Katsuhiko Hayashi, Anca Farcas, Kit-Wan Ma, Shinsuke Ito, Jafar Sharif, Tamie Endoh, Naoko Onaga, Manabu Nakayama, Tomoyuki Ishikura, Osamu Masui, Benedikt M Kessler, Toshio Suda, Osamu Ohara, Akihiko Okuda, Robert J Klose, Haruhiko Koseki
The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability...
March 17, 2017: ELife
https://www.readbyqxmd.com/read/28300060/h3-ubiquitination-by-nedd4-regulates-h3-acetylation-and-tumorigenesis
#3
Xian Zhang, Binkui Li, Abdol Hossein Rezaeian, Xiaohong Xu, Ping-Chieh Chou, Guoxiang Jin, Fei Han, Bo-Syong Pan, Chi-Yun Wang, Jie Long, Anmei Zhang, Chih-Yang Huang, Fuu-Jen Tsai, Chang-Hai Tsai, Christopher Logothetis, Hui-Kuan Lin
Dynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular importance. Here we show that, in a glucose-dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on lysine 23/36/37 residues, which specifically recruits histone acetyltransferase GCN5 for subsequent H3 acetylation. Genome-wide analysis of chromatin immunoprecipitation followed by sequencing reveals that NEDD4 regulates glucose-induced H3 K9 acetylation at transcription starting site and enhancer regions...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28298436/chromatin-remodeler-chd4-represses-aberrant-expression-of-tbx3-and-sustains-self-renewal-of-embryonic-stem-cells
#4
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of a series of transcriptional factors and epigenetic modulators. However, molecular mechanisms underlying the function of these regulators are not fully elucidated. Chd4, an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in the regulation of ESC properties remains elusive...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28294537/beyond-histones-the-expanding-roles-of-protein-lysine-methylation
#5
REVIEW
Zhouran Wu, Justin Connolly, Kyle K Biggar
A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation, and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code...
March 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28291796/the-effect-of-acetaminophen-on-ubiquitin-homeostasis-in-saccharomyces-cerevisiae
#6
Angelina Huseinovic, Jolanda S van Leeuwen, Tibor van Welsem, Iris Stulemeijer, Fred van Leeuwen, Nico P E Vermeulen, Jan M Kooter, J Chris Vos
Acetaminophen (APAP), although considered a safe drug, is one of the major causes of acute liver failure by overdose, and therapeutic chronic use can cause serious health problems. Although the reactive APAP metabolite N-acetyl-p-benzoquinoneimine (NAPQI) is clearly linked to liver toxicity, toxicity of APAP is also found without drug metabolism of APAP to NAPQI. To get more insight into mechanisms of APAP toxicity, a genome-wide screen in Saccharomyces cerevisiae for APAP-resistant deletion strains was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28286521/pulling-a-ligase-out-of-a-hat-pcaf-mediates-ubiquitination-of-the-class-ii-transactivator
#7
Julie E Morgan, Susanna F Greer
The Class II Transactivator (CIITA) is essential to the regulation of Major Histocompatibility Class II (MHC II) genes transcription. As the "master regulator" of MHC II transcription, CIITA regulation is imperative and requires various posttranslational modifications (PTMs) in order to facilitate its role. Previously we identified various ubiquitination events on CIITA. Monoubiquitination is important for CIITA transactivity, while K63 linked ubiquitination is involved in crosstalk with ERK1/2 phosphorylation, where together they mediate cellular movement from the cytoplasm to nuclear region...
2017: International Journal of Cell Biology
https://www.readbyqxmd.com/read/28283560/hdac7-ubiquitination-by-the-e3-ligase-cbx4-is-involved-in-contextual-fear-conditioning-memory-formation
#8
Xu Jing, Wen-Hai Sui, Shuai Wang, Xu-Feng Xu, Rong-Rong Yuan, Xiao-Rong Chen, Hui-Xian Ma, Ying-Xiao Zhu, Jin-Kai Sun, Fan Yi, Zhe-Yu Chen, Yue Wang
Histone acetylation, which comprises an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that HDAC inhibitors may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus (DH) of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4 h∼24 h), which was involved in long-term CFC memory formation...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28246399/usp7-dependent-histone-h3-deubiquitylation-regulates-maintenance-of-dna-methylation
#9
Luna Yamaguchi, Atsuya Nishiyama, Toshinori Misaki, Yoshikazu Johmura, Jun Ueda, Kyohei Arita, Koji Nagao, Chikashi Obuse, Makoto Nakanishi
Uhrf1-dependent histone H3 ubiquitylation plays a crucial role in the maintenance of DNA methylation via the recruitment of the DNA methyltransferase Dnmt1 to DNA methylation sites. However, the involvement of deubiquitylating enzymes (DUBs) targeting ubiquitylated histone H3 in the maintenance of DNA methylation is largely unknown. With the use of Xenopus egg extracts, we demonstrate here that Usp7, a ubiquitin carboxyl-terminal hydrolase, forms a stable complex with Dnmt1 and is recruited to DNA methylation sites during DNA replication...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28246327/monoubiquitylation-of-histone-h2b-contributes-to-the-bypass-of-dna-damage-during-and-after-dna-replication
#10
Shih-Hsun Hung, Ronald P Wong, Helle D Ulrich, Cheng-Fu Kao
DNA lesion bypass is mediated by DNA damage tolerance (DDT) pathways and homologous recombination (HR). The DDT pathways, which involve translesion synthesis and template switching (TS), are activated by the ubiquitylation (ub) of PCNA through components of the RAD6-RAD18 pathway, whereas the HR pathway is independent of RAD18 However, it is unclear how these processes are coordinated within the context of chromatin. Here we show that Bre1, an ubiquitin ligase specific for histone H2B, is recruited to chromatin in a manner coupled to replication of damaged DNA...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28240985/a-palb2-interacting-domain-in-rnf168-couples-homologous-recombination-to-dna-break-induced-chromatin-ubiquitylation
#11
Martijn S Luijsterburg, Dimitris Typas, Marie-Christine Caron, Wouter W Wiegant, Diana van den Heuvel, Rick A Boonen, Anthony M Couturier, Leon H Mullenders, Jean-Yves Masson, Haico van Attikum
DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur. With the inhibitory impact of RIF1 relieved, it remains unclear how RNF168-induced ubiquitylation influences HR. Here, we uncover that RNF168 links the HR machinery to H2A ubiquitylation in S/G2 cells...
February 27, 2017: ELife
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#12
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#13
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28209164/rnf40-regulates-gene-expression-in-an-epigenetic-context-dependent-manner
#14
Wanhua Xie, Sankari Nagarajan, Simon J Baumgart, Robyn Laura Kosinsky, Zeynab Najafova, Vijayalakshmi Kari, Magali Hennion, Daniela Indenbirken, Stefan Bonn, Adam Grundhoff, Florian Wegwitz, Ahmed Mansouri, Steven A Johnsen
BACKGROUND: Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively acting histone modification and that increased H2Bub1 occupancy correlates with increased gene expression. In contrast, depletion of the H2B ubiquitin ligases RNF20 or RNF40 alters the expression of only a subset of genes. RESULTS: Using conditional Rnf40 knockout mouse embryo fibroblasts, we show that genes occupied by low to moderate amounts of H2Bub1 are selectively regulated in response to Rnf40 deletion, whereas genes marked by high levels of H2Bub1 are mostly unaffected by Rnf40 loss...
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28188175/gcn5-determines-the-fate-of-drosophila-germline-stem-cells-through-degradation-of-cyclin-a
#15
Tianqi Liu, Qi Wang, Wenqing Li, Feiyu Mao, Shanshan Yue, Sun Liu, Xiaona Liu, Shan Xiao, Laixin Xia
The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood. The cell cycle of Drosophila female germline stem cells (GSCs) is characterized by short G1 and very long G2 phases, making it an excellent model for the study of cell cycle control in stem cell fate determination. Using a Drosophila female GSCs model, we found Gcn5, the first discovered histone acetyltransferase, to maintain germline stem cells in Drosophila ovaries...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28178526/crl4-dcaf8-ubiquitin-ligase-targets-histone-h3k79-and-promotes-h3k9-methylation-in-the-liver
#16
Gaofeng Li, Tong Ji, Jiang Chen, Yufei Fu, Lidan Hou, Yan Feng, Tingyue Zhang, Tianyu Song, Jie Zhao, Yoko Endo, Hui Lin, Xiujun Cai, Yong Cang
Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28166537/synthetic-essentiality-of-chromatin-remodelling-factor-chd1-in-pten-deficient-cancer
#17
Di Zhao, Xin Lu, Guocan Wang, Zhengdao Lan, Wenting Liao, Jun Li, Xin Liang, Jasper Robin Chen, Sagar Shah, Xiaoying Shang, Ming Tang, Pingna Deng, Prasenjit Dey, Deepavali Chakravarti, Peiwen Chen, Denise J Spring, Nora M Navone, Patricia Troncoso, Jianhua Zhang, Y Alan Wang, Ronald A DePinho
Synthetic lethality and collateral lethality are two well-validated conceptual strategies for identifying therapeutic targets in cancers with tumour-suppressor gene deletions. Here, we explore an approach to identify potential synthetic-lethal interactions by screening mutually exclusive deletion patterns in cancer genomes. We sought to identify 'synthetic-essential' genes: those that are occasionally deleted in some cancers but are almost always retained in the context of a specific tumour-suppressor deficiency...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28160502/deubiquitinating-enzyme-usp22-positively-regulates-c-myc-stability-and-tumorigenic-activity-in-mammalian-and-breast-cancer-cells
#18
Dongyeon Kim, Ahyoung Hong, Hye In Park, Woo Hyun Shin, Lang Yoo, Seo Jeong Jeon, Kwang Chul Chung
The proto-oncogene c-Myc has a pivotal function in growth control, differentiation and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression...
February 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28157208/rnf20-and-histone-h2b-ubiquitylation-exert-opposing-effects-in-basal-like-versus-luminal-breast-cancer
#19
Ohad Tarcic, Roy Z Granit, Ioannis S Pateras, Hadas Masury, Bella Maly, Yaara Zwang, Yosef Yarden, Vassilis G Gorgoulis, Eli Pikarsky, Ittai Ben-Porath, Moshe Oren
Breast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors...
February 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28139057/synthesis-of-ubiquitylated-histone-h3-using-a-thiirane-linker-for-chemical-ligation
#20
Toru Kawakami, Yuichi Mishima, Hironobu Hojo, Isao Suetake
Post-translational modifications of histone proteins, which form nucleosome cores, play an important role in gene regulation. Ubiquitin modification is one such modification. We previously reported on the use of a thiirane linker to introduce a 1,2-aminothiol moiety at a cysteine residue for native chemical ligation with peptide thioesters, which permitted isopeptide mimetics to be produced. In this report, we describe the preparation of the ubiquitylated full length histone H3 at the 18 position and the construction of tetranucleosomes with recombinant histones H2A, H2B, H4, and DNA, which are slightly more stable than those that are prepared without ubiquitin modification...
January 31, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
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