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Deborah J Marsh, Kristie-Ann Dickson
There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function as scaffolds or docking platforms for proteins involved in transcription or DNA repair; however, not all sites are equal, with some sites resulting in actively transcribed chromatin and others associated with gene silencing...
January 18, 2019: Genes
Siqi Ma, Ning Tang, Xu Li, Yongjun Xie, Denghao Xiang, Jie Fu, Jianqiang Shen, Jun Yang, Haifu Tu, Xianghua Li, Honghong Hu, Lizhong Xiong
Histone H2B monoubiquitination (H2Bub1) has been implicated in several important physiological and developmental processes, but its role in the regulation of plant stress responses remains elusive. Here, we report that H2Bub1 is crucially involved in abscisic acid (ABA) signaling and drought response in rice. We found the rice HISTONE MONOUBIQUITINATION2 (OsHUB2), an E3 ligase for H2Bub1, interacted with OsbZIP46, a key transcription factor regulating ABA signaling and drought response in rice. Genetic analyses suggest that OsHUB2, up-regulated by drought and ABA, positively modulates ABA sensitivity and drought resistance...
December 19, 2018: Molecular Plant
Jagmohan Hooda, Marian Novak, Matthew P Salomon, Chikako Matsuba, Romela I Ramos, Emily MacDuffie, Melissa Song, Michelle S Hirsch, Jenny Lester, Vinita Parkash, Beth Y Karlan, Moshe Oren, Dave S Hoon, Ronny Drapkin
Recent insights supporting the fallopian tube epithelium (FTE) and serous tubal intraepithelial carcinomas (STIC) as the tissue of origin and the precursor lesion, respectively, for the majority of high-grade serous ovarian carcinomas (HGSOC) provide the necessary context to study the mechanisms that drive the development and progression of HGSOC. Here we investigate the role of the E3 ubiquitin ligase RNF20 and histone H2B monoubiquitylation (H2Bub1) in serous tumorigenesis and report that heterozygous loss of RNF20 defines the majority of HGSOC tumors...
December 18, 2018: Cancer Research
Youbao Zhao, Srijana Upadhyay, Xiaorong Lin
Switching between different morphotypes is an adaptive cellular response in many microbes. In Cryptococcus neoformans , the yeast-to-hypha transition confers resistance to microbial predation in the soil and is an integral part of its life cycle. Morphogenesis is also known to be associated with virulence, with the filamentous form being immune-stimulatory and protective in mammalian models of cryptococcosis. Previous studies identified the transcription factor Znf2 as a master regulator of cryptococcal filamentation...
November 13, 2018: MBio
Robyn Laura Kosinsky, Robert Lorenz Chua, Martin Qui, Dominik Saul, Dawid Mehlich, Philipp Ströbel, Hans-Ulrich Schildhaus, Florian Wegwitz, William A Faubion, Steven A Johnsen
Background and Aims: Inflammatory bowel diseases are linked to an increased risk of developing colorectal cancer (CRC). Previous studies suggested that the H2B ubiquitin ligase RING finger protein-20 (RNF20) inhibited inflammatory signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, the role of RNF40, the obligate heterodimeric partner of RNF20, in the context of inflammation and CRC has not been addressed. Here, we examined the effect of RNF40 loss on CRC cells in vitro and on inflammation and inflammatory signaling in vitro and in vivo...
October 13, 2018: Journal of Crohn's & Colitis
Zhenfang Wu, Ming-Hong He, Ling-Li Zhang, Jun Liu, Qiong-Di Zhang, Jin-Qiu Zhou
Histone H2B lysine 123 mono-ubiquitination (H2Bub1), catalyzed by Rad6 and Bre1 in Saccharomyces cerevisiae, modulates chromatin structure and affects diverse cellular functions. H2Bub1 plays roles in telomeric silencing and telomere replication. Here, we have explored a novel role of H2Bub1 in telomere protection at uncapped telomeres in yku70Δ and cdc13-1 cells. Deletion of RAD6 or BRE1, or mutation of H2BK123R enhances the temperature sensitivity of both yku70Δ and cdc13-1 telomere capping mutants. Consistently, BRE1 deletion increases accumulation of telomeric single-stranded DNA (ssDNA) in yku70Δ and cdc13-1 cells, and EXO1 deletion improves the growth of yku70Δ bre1Δ and cdc13-1 bre1Δ cells and decreases ssDNA accumulation...
September 17, 2018: DNA Repair
Paula Oliete-Calvo, Joan Serrano-Quílez, Carme Nuño-Cabanes, María E Pérez-Martínez, Luis M Soares, Bernhard Dichtl, Stephen Buratowski, José E Pérez-Ortín, Susana Rodríguez-Navarro
Monoubiquitination of histone H2B (to H2Bub1) is required for downstream events including histone H3 methylation, transcription, and mRNA export. The mechanisms and players regulating these events have not yet been completely delineated. Here, we show that the conserved Ran-binding protein Mog1 is required to sustain normal levels of H2Bub1 and H3K4me3 in Saccharomyces cerevisiae Mog1 is needed for gene body recruitment of Rad6, Bre1, and Rtf1 that are involved in H2B ubiquitination and genetically interacts with these factors...
November 2018: EMBO Reports
Hong Chen, Hao Feng, Xueyan Zhang, Chaojun Zhang, Tao Wang, Jiangli Dong
The HUB2 gene encoding histone H2B monoubiquitination E3 ligase is involved in seed dormancy, flowering timing, defence response and salt stress regulation in Arabidopsis thaliana. In this study, we used the cauliflower mosaic virus (CaMV) 35S promoter to drive AtHUB2 overexpression in cotton and found that it can significantly improve the agricultural traits of transgenic cotton plants under drought stress conditions, including increasing the fruit branch number, boll number, and boll-setting rate and decreasing the boll abscission rate...
August 17, 2018: Plant Biotechnology Journal
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)...
October 1, 2018: Journal of Cell Biology
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
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
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
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
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
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
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
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
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
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
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
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