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histone ubiquitination

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https://www.readbyqxmd.com/read/27923209/recognition-of-ubiquitinated-nucleosomes
#1
REVIEW
Michael T Morgan, Cynthia Wolberger
Histone ubiquitination plays a non-degradative role in regulating transcription and the DNA damage response. A mechanistic understanding of this chromatin modification has lagged that of small histone modifications because of the technical challenges in preparing ubiquitinated nucleosomes. The recent structure of the DUB module of the SAGA coactivator complex bound to a nucleosome containing monoubiquitinated H2B has provided the first view of how specialized subunits target this enzyme to its substrate. Single particle electron microscopy of the intact SAGA coactivator suggests how the DUB module and histone acetyltransferase module engage a nucleosomal substrate...
December 3, 2016: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/27922451/direct-screening-for-chromatin-status-on-dna-barcodes-in-yeast-delineates-the-regulome-of-h3k79-methylation-by-dot1
#2
Hanneke Vlaming, Thom M Molenaar, Tibor van Welsem, Deepani W Poramba-Liyanage, Desiree E Smith, Arno Velds, Liesbeth Hoekman, Tessy Korthout, Sjoerd Hendriks, Af Maarten Altelaar, Fred van Leeuwen
Given the frequent misregulation of chromatin in cancer, it is important to understand the cellular mechanisms that regulate chromatin structure. However, systematic screening for epigenetic regulators is challenging and often relies on laborious assays or indirect reporter read-outs. Here we describe a strategy, Epi-ID, to directly assess chromatin status in thousands of mutants. In Epi-ID, chromatin status on DNA barcodes is interrogated by chromatin immunoprecipitation followed by deep sequencing, allowing for quantitative comparison of many mutants in parallel...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27892467/jarid2-binds-mono-ubiquitylated-h2a-lysine-119-to-mediate-crosstalk-between-polycomb-complexes-prc1-and-prc2
#3
Sarah Cooper, Anne Grijzenhout, Elizabeth Underwood, Katia Ancelin, Tianyi Zhang, Tatyana B Nesterova, Burcu Anil-Kirmizitas, Andrew Bassett, Susanne M Kooistra, Karl Agger, Kristian Helin, Edith Heard, Neil Brockdorff
The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27886188/the-deubiquitinase-usp21-maintains-the-stemness-of-mouse-embryonic-stem-cells-via-stabilization-of-nanog
#4
Jiali Jin, Jian Liu, Cong Chen, Zhenping Liu, Cong Jiang, Hongshang Chu, Weijuan Pan, Xinbo Wang, Lingqiang Zhang, Bin Li, Cizhong Jiang, Xin Ge, Xin Xie, Ping Wang
Nanog is a master pluripotency factor of embryonic stem cells (ESCs). Stable expression of Nanog is essential to maintain the stemness of ESCs. However, Nanog is a short-lived protein and quickly degraded by the ubiquitin-dependent proteasome system. Here we report that the deubiquitinase USP21 interacts with, deubiquitinates and stabilizes Nanog, and therefore maintains the protein level of Nanog in mouse ESCs (mESCs). Loss of USP21 results in Nanog degradation, mESCs differentiation and reduces somatic cell reprogramming efficiency...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27884978/estrogen-receptor-negativity-in-breast-cancer-a-cause-or-consequence
#5
Vijaya Narasihma Reddy Gajulapalli, Vijaya Lakshmi Malisetty, Suresh Kumar Chitta, Bramanandam Manavathi
Endocrine resistance, which occurs either by de novo or acquired route, is posing a major challenge in treating hormone-dependent breast cancers by endocrine therapies. The loss of ERα expression is the vital cause of establishing endocrine resistance in this subtype. Understanding the mechanisms that determine the causes of this phenomenon are therefore essential to reduce the disease efficacy. But how we negate estrogen receptor (ER) negativity and endocrine resistance in breast cancer is questionable, to answer that two important approaches are considered: 1) Understanding the cellular origin of heterogeneity and ER negativity in breast cancers, and 2) characterization of molecular regulators of endocrine resistance...
November 24, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27880725/mouse-sirt3-promotes-autophagy-in-angii-induced-myocardial-hypertrophy-through-the-deacetylation-of-foxo1
#6
Jingyuan Li, Tongshuai Chen, Ming Xiao, Na Li, Shujian Wang, Hongyan Su, Xiaobin Guo, Hui Liu, Fangying Yan, Yi Yang, Yun Zhang, Peili Bu
Sirt3, a mitochondrial NAD+-dependent histone deacetylase, is the only member proven to promote longevity in mammalian Sirtuin family. The processed short form of Sirt3 has been demonstrated to target many mediators of energy metabolism and mitochondrial stress adaptive program. Autophagy serves as a dynamic recycling mechanism and provides energy or metabolic substrates. Among the mechanisms triggered by cardiac stress, opinions vary as to whether autophagy is a protective or detrimental response. Here, by inducing the Sirt3-knockout mice to myocardial hypertrophy with chronic angiotensin II infusion for four weeks, we determined the role of Sirt3 in myocardial hypertrophy and autophagy...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27875543/irisin-ameliorates-hypoxia-reoxygenation-induced-injury-through-modulation-of-histone-deacetylase-4
#7
Yu Tina Zhao, Hao Wang, Shouyan Zhang, Jianfeng Du, Shougang Zhuang, Ting C Zhao
Irisin is a recently identified myokine which brings increases in energy expenditure and contributes to the beneficial effects of exercise through the browning of white adipose tissues. However, its effects in the heart remains unknown. This study sought to determine the effects of irisin on hypoxia/reoxygenation injury and its relationship with HDAC4. Wild type and stable HDAC4-overexpression cells were generated from H9c2 cardiomyoblasts. HDAC4 overexpression cells and wild type H9c2 cells were exposed to 24 hours of hypoxia followed by one hour of reoxygenation in vitro in the presence or absence of irisin (5 ng/ml)...
2016: PloS One
https://www.readbyqxmd.com/read/27870837/ubiquitin-utilizes-an-acidic-surface-patch-to-alter-chromatin-structure
#8
Galia T Debelouchina, Karola Gerecht, Tom W Muir
Ubiquitylation of histone H2B, associated with gene activation, leads to chromatin decompaction through an unknown mechanism. We used a hydrogen-deuterium exchange strategy coupled with NMR spectroscopy to map the ubiquitin surface responsible for its structural effects on chromatin. Our studies revealed that a previously uncharacterized acidic patch on ubiquitin comprising residues Glu16 and Glu18 is essential for decompaction. These residues mediate promiscuous electrostatic interactions with the basic histone proteins, potentially positioning the ubiquitin moiety as a dynamic 'wedge' that prevents the intimate association of neighboring nucleosomes...
November 21, 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27869166/skp2-loss-destabilizes-ezh2-by-promoting-traf6-mediated-ubiquitination-to-suppress-prostate-cancer
#9
W Lu, S Liu, B Li, Y Xie, M G Izban, B R Ballard, S A Sathyanarayana, S E Adunyah, R J Matusik, Z Chen
EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues...
November 21, 2016: Oncogene
https://www.readbyqxmd.com/read/27857976/autophagy-regulates-dna-repair-by-modulating-histone-ubiquitination
#10
Yanan Wang, Wei-Guo Zhu, Ying Zhao
Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. Here, we report that the autophagy receptor and substrate p62/SQSTM1 inhibits DNA double-strand break -induced histone and chromatin ubiquitination, which has a critical role in attracting key repair factors to the break sites.
2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27832544/in-vitro-assay-to-study-histone-ubiquitination-during-transcriptional-regulation
#11
Jogender Tushir-Singh, Sanchita Bhatnagar
In mammals, gene expression is largely controlled at the transcriptional level. In response to environmental or intrinsic signaling, gene expression is often fine-tuned by epigenetic modifications, including DNA methylation and histone modifications. One such histone modification is ubiquitination that predominately occurs in mono-ubiquitinated forms on histone H2A and H2B. We recently identified and characterized a novel E3 ligase called TRIM37 that ubiquitinates H2A. This study highlights the consequence of aberrant histone ubiquitination at the promoters of tumor suppressor genes in breast cancer...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27825134/interleukin-13-suppresses-interleukin-10-via-inhibiting-a20-in-peripheral-b-cells-of-patients-with-food-allergy
#12
Ming-Yang Li, Min Zhu, En-Qiang Linghu, Fan Feng, Bing Zhu, Cheng Wu, Ming-Zhou Guo
The regulatory B cells (Breg) are important in the body immunity. The differentiation process of Breg is not fully understood yet. Ubiquitin A20 has immune regulatory functions. This study aims to investigate the role of A20 in the regulation of interleukin (IL)-10 in B cells. In this study, B cells were isolated from the peripheral blood samples of healthy subjects and patients with food allergy (FA). The B cells were analyzed by flow cytometry, real time RT-PCR, Western blotting and chromatin immunoprecipitation...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27798683/ubiquitination-of-lysine-867-of-the-human-setdb1-protein-upregulates-its-histone-h3-lysine-9-h3k9-methyltransferase-activity
#13
Kenji Ishimoto, Natsuko Kawamata, Yoshie Uchihara, Moeka Okubo, Reiko Fujimoto, Eiko Gotoh, Keisuke Kakinouchi, Eiichi Mizohata, Nobumasa Hino, Yoshiaki Okada, Yasuhiro Mochizuki, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Tsuyoshi Inoue, Keisuke Tachibana, Takefumi Doi
Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1...
2016: PloS One
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
#14
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...
October 25, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27794026/histone-h4-facilitates-the-proteolysis-of-the-budding-yeast-cenp-acse4-centromeric-histone-variant
#15
Gary M R Deyter, Erica M Hildebrand, Adrienne D Barber, Sue Biggins
The incorporation of histone variants into nucleosomes can alter chromatin-based processes. CENP-A is the histone H3 variant found exclusively at centromeres that serves as an epigenetic mark for centromere identity and is required for kinetochore assembly. CENP-A mislocalization to ectopic sites appears to contribute to genomic instability, transcriptional misregulation, and tumorigenesis, so mechanisms exist to ensure its exclusive localization to centromeres. One conserved process is proteolysis, which is mediated by the Psh1 E3 ubiquitin ligase in Saccharomyces cerevisiae (budding yeast)...
October 28, 2016: Genetics
https://www.readbyqxmd.com/read/27791533/autophagy-substrate-sqstm1-p62-regulates-chromatin-ubiquitination-during-the-dna-damage-response
#16
Yanan Wang, Wei-Guo Zhu, Ying Zhao
The importance of autophagy in the DNA damage repair process is clear; however, the detailed molecular mechanism is still largely unknown. Here we found that DNA damage-induced histone H2A ubiquitination is suppressed in autophagy-deficient cells in a SQSTM1/p62 dependent manner. SQSTM1 binds and inhibits E3 ligase RNF168s activity, which is essential for H2A ubiquitination. As a result, several important factors for DNA repair cannot be recruited to the sites of DNA double-strand breaks (DSBs) in autophagy-deficient cells, leading to diminished DNA repair and increased sensitivity of cells to radiation...
October 28, 2016: Autophagy
https://www.readbyqxmd.com/read/27783058/ubiquitin-in-influenza-virus-entry-and-innate-immunity
#17
REVIEW
Alina Rudnicka, Yohei Yamauchi
Viruses are obligatory cellular parasites. Their mission is to enter a host cell, to transfer the viral genome, and to replicate progeny whilst diverting cellular immunity. The role of ubiquitin is to regulate fundamental cellular processes such as endocytosis, protein degradation, and immune signaling. Many viruses including influenza A virus (IAV) usurp ubiquitination and ubiquitin-like modifications to establish infection. In this focused review, we discuss how ubiquitin and unanchored ubiquitin regulate IAV host cell entry, and how histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase with ubiquitin-binding activity, mediates IAV capsid uncoating...
October 24, 2016: Viruses
https://www.readbyqxmd.com/read/27780782/atprmt5-regulates-shoot-regeneration-through-mediating-histone-h4r3-dimethylation-on-krps-and-pre-mrna-splicing-of-rkp-in-arabidopsis
#18
Hui Liu, Xu Ma, Hua Nan Han, Yu Jin Hao, Xian Sheng Zhang
Protein arginine methylation plays important roles in diverse biological processes, but its role in regulating shoot regeneration remains elusive. In this study, we characterized the function of the protein arginine methyltransferase AtPRMT5 during de novo shoot regeneration in Arabidopsis. AtPRMT5 encodes a type II protein arginine methyltransferase that methylates proteins, including histones and RNA splicing factors. The frequency of shoot regeneration and the number of shoots per callus were decreased in the atprmt5 mutant compared with those in the wild type...
December 5, 2016: Molecular Plant
https://www.readbyqxmd.com/read/27773672/cyclin-f-mediated-degradation-of-slbp-limits-h2a-x-accumulation-and-apoptosis-upon-genotoxic-stress-in-g2
#19
John F Dankert, Gergely Rona, Linda Clijsters, Phillip Geter, Jeffrey R Skaar, Keria Bermudez-Hernandez, Elizabeth Sassani, David Fenyö, Beatrix Ueberheide, Robert Schneider, Michele Pagano
SLBP (stem-loop binding protein) is a highly conserved factor necessary for the processing, translation, and degradation of H2AFX and canonical histone mRNAs. We identified the F-box protein cyclin F, a substrate recognition subunit of an SCF (Skp1-Cul1-F-box protein) complex, as the G2 ubiquitin ligase for SLBP. SLBP interacts with cyclin F via an atypical CY motif, and mutation of this motif prevents SLBP degradation in G2. Expression of an SLBP stable mutant results in increased loading of H2AFX mRNA onto polyribosomes, resulting in increased expression of H2A...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#20
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
October 15, 2016: EBioMedicine
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