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H2Bub1

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https://www.readbyqxmd.com/read/30054449/transcription-and-mrna-export-machineries-saga-and-trex-2-maintain-monoubiquitinated-h2b-balance-required-for-dna-repair
#1
Federica M Evangelista, Anne Maglott-Roth, Matthieu Stierle, Laurent Brino, Evi Soutoglou, László Tora
DNA repair is critical to maintaining genome integrity, and its dysfunction can cause accumulation of unresolved damage that leads to genomic instability. The Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator complex and the nuclear pore-associated transcription and export complex 2 (TREX-2) couple transcription with mRNA export. In this study, we identify a novel interplay between human TREX-2 and the deubiquitination module (DUBm) of SAGA required for genome stability. We find that the scaffold subunit of TREX-2, GANP, positively regulates DNA repair through homologous recombination (HR)...
July 27, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29934362/role-of-rnf20-in-cancer-development-and-progression-a-comprehensive-review
#2
REVIEW
Gautam Sethi, Muthu K Shanmugam, Frank Arfuso, Alan Prem Kumar
Evolving strategies to counter cancer initiation and progression rely on the identification of novel therapeutic targets that exploit the aberrant genetic changes driving oncogenesis. Several chromatin associated enzymes have been shown to influence post-translational modification (PTM) in DNA, histones, and non-histone proteins. Any deregulation of this core group of enzymes often leads to cancer development. Ubiquitylation of histone H2B in mammalian cells was identified over three decades ago. An exciting really interesting new gene (RING) family of E3 ubiquitin ligases, known as RNF20 and RNF40, monoubiquitinates histone H2A at K119 or H2B at K120, is known to function in transcriptional elongation, DNA double-strand break (DSB) repair processes, maintenance of chromatin differentiation, and exerting tumor suppressor activity...
August 31, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29720480/targeting-usp22-suppresses-tumorigenicity-and-enhances-cisplatin-sensitivity-through-aldh1a3-downregulation-in-cancer-initiating-cells-from-lung-adenocarcinoma
#3
Xinwei Yun, Keqiang Zhang, Jinhui Wang, Rajendra P Pangeni, Lu Yang, Melissa Bonner, Jun Wu, Jami Wang, Isaac K Nardi, Ming Gao, Dan J Raz
Loss of monoubiquitination of histone H2B (H2Bub1) was found to be associated with poor-differentiation and enhanced malignancy of lung adenocarcinoma. This study investigated the association and impact of the ubiquitin-specific peptidase 22 (USP22), an H2Bub1 deubiquitinase, on stem cell-like characteristics and cisplatin resistance in cancer-initiating cells (CIC) from primary lung adenocarcinoma. CICs were isolated, enriched, and characterized from patient-derived cancer tissues using both in vitro tumorsphere formation and in vivo xenograft assays...
July 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29274341/the-ubiquitin-specific-protease-usp36-is-a-conserved-histone-h2b-deubiquitinase
#4
Tiffany DeVine, Rosalie C Sears, Mu-Shui Dai
Histone H2B monoubiquitination plays a critical role in the regulation of gene transcription. Deregulation of H2B monoubiquitination contributes to human pathologies, such as cancer. Here we report that human USP36 is a novel H2Bub1 deubiquitinase. We show that USP36 interacts with H2B and deubiquitinates H2Bub1 in cells and in vitro. Overexpression of USP36 markedly reduced the levels of H2Bub1 in cells. Using the p21 gene as a model, we demonstrate that depletion of USP36 increases H2Bub1 at the p21 locus, primarily within its gene body...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29210986/ubiquitin-specific-peptidase-22-regulates-histone-h2b-mono-ubiquitination-and-exhibits-both-oncogenic-and-tumor-suppressor-roles-in-cancer
#5
REVIEW
Lucile M-P Jeusset, Kirk J McManus
Ubiquitin-Specific Peptidase 22 (USP22) is a ubiquitin hydrolase, notably catalyzing the removal of the mono-ubiquitin moiety from histone H2B (H2Bub1). Frequent overexpression of USP22 has been observed in various cancer types and is associated with poor patient prognosis. Multiple mechanisms have been identified to explain how USP22 overexpression contributes to cancer progression, and thus, USP22 has been proposed as a novel drug target in cancer. However, gene re-sequencing data from numerous cancer types show that USP22 expression is frequently diminished, suggesting it may also harbor tumor suppressor-like properties...
December 6, 2017: Cancers
https://www.readbyqxmd.com/read/29058668/e3-ubiquitin-ligase-bre1-couples-sister-chromatid-cohesion-establishment-to-dna-replication-in-saccharomyces-cerevisiae
#6
Wei Zhang, Clarence Hue Lok Yeung, Liwen Wu, Karen Wing Yee Yuen
Bre1, a conserved E3 ubiquitin ligase in Saccharomyces cerevisiae , together with its interacting partner Lge1, are responsible for histone H2B monoubiquitination, which regulates transcription, DNA replication, and DNA damage response and repair, ensuring the structural integrity of the genome. Deletion of BRE1 or LGE1 also results in whole chromosome instability. We discovered a novel role for Bre1, Lge1 and H2Bub1 in chromosome segregation and sister chromatid cohesion. Bre1's function in G1 and S phases contributes to cohesion establishment, but it is not required for cohesion maintenance in G2 phase...
October 23, 2017: ELife
https://www.readbyqxmd.com/read/28984873/rnf20-controls-astrocytic-differentiation-through-epigenetic-regulation-of-stat3-in-the-developing-brain
#7
Qingli Liang, Wenlong Xia, Wei Li, Jianwei Jiao
Astrocyte has crucial roles in the central nervous system and accumulating evidence has shown its core function for brain complexity, plasticity and cognition. However, the essential key factors in the precise regulation of astrocytic differentiation remain largely uncharacterized. Here, we identified that RNF20, an E3 ligase of H2BK120 in the mammalian system, regulates astrocyte production from neural precursor cells. RNF20 deficiency by shRNA knockdown or deletion in conditional knockout mice impairs the astrocytic differentiation...
February 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28604753/let-7b-and-let-7c-micrornas-promote-histone-h2b-ubiquitylation-and-inhibit-cell-migration-by-targeting-multiple-components-of-the-h2b-deubiquitylation-machinery
#8
A Spolverini, G Fuchs, D R Bublik, M Oren
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer...
October 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28481029/loss-of-h2b-monoubiquitination-is-associated-with-poor-differentiation-and-enhanced-malignancy-of-lung-adenocarcinoma
#9
Keqiang Zhang, Jinhui Wang, Tommy R Tong, Xiwei Wu, Rebecca Nelson, Yate-Ching Yuan, Theresa Reno, Zheng Liu, Xinwei Yun, Jae Y Kim, Ravi Salgia, Dan J Raz
Deregulated monoubiquitination of histone H2B (H2Bub1), mainly catalyzed by E3 ubiquitin-protein ligase RNF20/RNF40 complex, may play an important role in cancer. Here we investigate potential roles of H2Bub1 and the underlying mechanisms through which it contributes to cancer development and progression in lung adenocarcinoma. We show that downregulation of H2Bub1 through RNF20 knockdown dramatically decreases H3K79 and H3K4 trimethylation in both normal and malignant lung epithelial cell lines. Concurrently, global transcriptional profiling analysis reveals that multiple tumor-associated genes such as CCND3, E2F1/2, HOXA1, Bcl2 modifying factor (BMF), Met, and Myc; and signaling pathways of cellular dedifferentiation, proliferation, adhesion, survival including p53, cadherin, Myc, and anti-apoptotic pathways are differentially expressed or significantly altered in these lung epithelial cells upon downregulation of H2Bub1...
August 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28453857/fbxl19-recruitment-to-cpg-islands-is-required-for-rnf20-mediated-h2b-mono-ubiquitination
#10
Bum-Kyu Lee, Jiwoon Lee, Wenwen Shen, Catherine Rhee, Haewon Chung, Jonghwan Kim
Histone H2B lysine 120 mono-ubiquitination (H2Bub1) catalyzed by Rnf20 has been implicated in normal differentiation of embryonic stem (ES) and adult stem cells. However, it remains unknown how Rnf20 is recruited to its specific target chromosomal loci for the establishment of H2Bub1. Here, we reveal that Fbxl19, a CxxC domain-containing protein, promotes H2Bub1 at the promoters of CpG island-containing genes by interacting with Rnf20. We show that up-regulation of Fbxl19 increases the level of global H2Bub1 in mouse ES cells, while down-regulation of Fbxl19 reduces the level of H2Bub1...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28453430/h2b-monoubiquitination-t-ub-or-not-t-ub-for-inducible-enhancers
#11
Gregory Segala, Didier Picard
Recently, we reported the unexpected finding that the monoubiquitination of histone H2B (H2Bub1) regulates inducible enhancers. Here, we propose a conceptual framework to reconcile the apparently discrepant roles of H2Bub1 in transcription initiation and elongation, and we discuss how H2Bub1 could regulate cellular processes linked to non-coding transcription.
March 15, 2017: Transcription
https://www.readbyqxmd.com/read/28337773/histone-h2b-monoubiquitination-regulates-salt-stress-induced-microtubule-depolymerization-in-arabidopsis
#12
Sa Zhou, Qiuhong Chen, Yuhui Sun, Yingzhang Li
Histone H2B monoubiquitination (H2Bub1) is recognized as a regulatory mechanism that controls a range of cellular processes. We previously showed that H2Bub1 was involved in responses to biotic stress in Arabidopsis. However, the molecular regulatory mechanisms of H2Bub1 in controlling responses to abiotic stress remain limited. Here, we report that HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 played important regulatory roles in response to salt stress. Phenotypic analysis revealed that H2Bub1 mutants confer decreased tolerance to salt stress...
August 2017: Plant, Cell & Environment
https://www.readbyqxmd.com/read/28209164/rnf40-regulates-gene-expression-in-an-epigenetic-context-dependent-manner
#13
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/28180298/histone-h2b-monoubiquitination-is-a-critical-epigenetic-switch-for-the-regulation-of-autophagy
#14
Su Chen, Yuanya Jing, Xuan Kang, Lu Yang, Da-Liang Wang, Wei Zhang, Lei Zhang, Ping Chen, Jian-Feng Chang, Xiao-Mei Yang, Fang-Lin Sun
Autophagy is an evolutionarily conserved cellular process that primarily participates in lysosome-mediated protein degradation. Although autophagy is a cytoplasmic event, how epigenetic pathways are involved in the regulation of autophagy remains incompletely understood. Here, we found that H2B monoubiquitination (H2Bub1) is down-regulated in cells under starvation conditions and that the decrease in H2Bub1 results in the activation of autophagy. We also identified that the deubiquitinase USP44 is responsible for the starvation-induced decrease in H2Bub1...
February 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28180293/rad6-bre1-mediated-h2b-ubiquitination-regulates-telomere-replication-by-promoting-telomere-end-resection
#15
Zhenfang Wu, Jun Liu, Qiong-Di Zhang, De-Kang Lv, Nian-Feng Wu, Jin-Qiu Zhou
Rad6 and Bre1, ubiquitin-conjugating E2 and E3 enzymes respectively, are responsible for histone H2B lysine 123 mono-ubiquitination (H2Bub1) in Saccharomyces cerevisiae. Previous studies have shown that Rad6 and Bre1 regulate telomere length and recombination. However, the underlying molecular mechanism remains largely unknown. Here we report that H2BK123 mutation results in telomere shortening, while inactivation of Ubp8 and/or Ubp10, deubiquitinases of H2Bub1, leads to telomere lengthening in Rad6-Bre1-dependent manner...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28157208/rnf20-and-histone-h2b-ubiquitylation-exert-opposing-effects-in-basal-like-versus-luminal-breast-cancer
#16
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...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27880911/usp44-is-an-integral-component-of-n-cor-that-contributes-to-gene-repression-by-deubiquitinating-histone-h2b
#17
Xianjiang Lan, Boyko S Atanassov, Wenqian Li, Ying Zhang, Laurence Florens, Ryan D Mohan, Paul J Galardy, Michael P Washburn, Jerry L Workman, Sharon Y R Dent
Decreased expression of the USP44 deubiquitinase has been associated with global increases in H2Bub1 levels during mouse embryonic stem cell (mESC) differentiation. However, whether USP44 directly deubiquitinates histone H2B or how its activity is targeted to chromatin is not known. We identified USP44 as an integral subunit of the nuclear receptor co-repressor (N-CoR) complex. USP44 within N-CoR deubiquitinates H2B in vitro and in vivo, and ablation of USP44 impairs the repressive activity of the N-CoR complex...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27798111/the-ring-finger-domain-e3-ubiquitin-ligases-brca1-and-the-rnf20-rnf40-complex-in-global-loss-of-the-chromatin-mark-histone-h2b-monoubiquitination-h2bub1-in-cell-line-models-and-primary-high-grade-serous-ovarian-cancer
#18
Kristie-Ann Dickson, Alexander J Cole, Anthony J Gill, Adele Clarkson, Gregory B Gard, Angela Chou, Catherine J Kennedy, Beric R Henderson, Sian Fereday, Nadia Traficante, Kathryn Alsop, David D Bowtell, Anna deFazio, Roderick Clifton-Bligh, Deborah J Marsh
Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells...
December 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27789696/histone-h2b-monoubiquitination-is-a-critical-epigenetic-switch-for-the-regulation-of-autophagy
#19
Su Chen, Yuanya Jing, Xuan Kang, Lu Yang, Da-Liang Wang, Wei Zhang, Lei Zhang, Ping Chen, Jian-Feng Chang, Xiao-Mei Yang, Fang-Lin Sun
Autophagy is an evolutionarily conserved cellular process that primarily participates in lysosome-mediated protein degradation. Although autophagy is a cytoplasmic event, how epigenetic pathways are involved in the regulation of autophagy remains incompletely understood. Here, we found that H2B monoubiquitination (H2Bub1) is down-regulated in cells under starvation conditions and that the decrease in H2Bub1 results in the activation of autophagy. We also identified that the deubiquitinase USP44 is responsible for the starvation-induced decrease in H2Bub1...
October 26, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27692985/monoubiquitination-of-histone-h2b-blocks-eviction-of-histone-variant-h2a-z-from-inducible-enhancers
#20
Gregory Segala, Marcela A Bennesch, Deo Prakash Pandey, Nicolas Hulo, Didier Picard
Covalent modifications of histones play a crucial role in the regulation of gene expression. Histone H2B monoubiquitination has mainly been described as a regulator of transcription elongation, but its role in transcription initiation is poorly documented. We investigated the role of this histone mark (H2Bub1) on different inducible enhancers, in particular those regulated by estrogen receptor α, by loss- and gain-of-function experiments with the specific E3-ubiquitin ligase complex of H2B: RNF20/RNF40. RNF20/RNF40 overexpression causes repression of the induced activity of these enhancers...
October 20, 2016: Molecular Cell
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