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Epigenetics and h2b

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https://www.readbyqxmd.com/read/28703681/activation-of-gene-expression-by-histone-deubiquitinase-otld1
#1
Ido Keren, Vitaly Citovsky
One of the main mechanisms of epigenetic control is post translational modification of histones, and one of the relatively less characterized, yet functionally important histone modifications is monoubiquitylation, which is reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a transcriptional repressor. But, could the same deubiquitinase act both as a repressor and an activator? Here, we addressed this question...
July 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28690313/the-hdac-inhibitor-panobinostat-lbh589-exerts-in-vivo-anti-leukaemic-activity-against-mll-rearranged-acute-lymphoblastic-leukaemia-and-involves-the-rnf20-rnf40-wac-h2b-ubiquitination-axis
#2
P G Castro, E H J van Roon, S S M Pinhanços, L Trentin, P Schneider, M Kerstjens, G Te Kronnie, O Heidenreich, R Pieters, R W Stam
MLL-rearranged acute lymphoblastic leukaemia (ALL) represents an aggressive malignancy in infants (<1 year of age), associated with poor outcome. Current treatment intensification is not further possible, and novel therapy strategies are needed. Notably, MLL-rearranged ALL is characterised by a strongly deregulated epigenome and shows sensitivity to epigenetic perturbators. Here, we demonstrate the in vivo efficacy of the histone deacetylase inhibitor Panobinostat (LHB589) using xenograft mouse models of MLL-rearranged ALL...
July 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28648780/the-histone-acetyltransferase-mst2-protects-active-chromatin-from-epigenetic-silencing-by-acetylating-the-ubiquitin-ligase-brl1
#3
Valentin Flury, Paula Raluca Georgescu, Vytautas Iesmantavicius, Yukiko Shimada, Tahsin Kuzdere, Sigurd Braun, Marc Bühler
Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals are not well understood. Here we report a positive feedback loop that preserves the transcription-competent state of RNA polymerase II-transcribed genes. We found that Pdp3 recruits the histone acetyltransferase Mst2 to H3K36me3-marked chromatin...
June 14, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28601081/histone-modifications-on-the-promoters-of-human-oct4-and-nanog-genes-at-the-onset-of-neural-differentiation-of-nt2-d1-cells
#4
V Topalovic, M Schwirtlich, M Stevanovic, M Mojsin
Transcription factors OCT4 and NANOG are main constituents of a functional network that controls proliferation and pluripotency maintenance of stem cells as well as early lineage decisions. We investigated expression profiles of OCT4 and NANOG during the early phases of neural differentiation using NT2/D1 cells induced by retinoic acid as an in vitro model system of human neurogenesis. We demonstrated decrease in OCT4 and NANOG mRNA and protein levels following exposure to retinoic acid. Next, by employing chromatin immunoprecipitation, we investigated profiles of selected H3 and H2B histone marks deposited on the promoters of the OCT4 and NANOG genes...
June 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28520954/h2b-ubiquitylation-and-the-histone-chaperone-asf1-cooperatively-mediate-the-formation-and-maintenance-of-heterochromatin-silencing
#5
Meng-Ying Wu, Chia-Yeh Lin, Hsin-Yi Tseng, Fei-Man Hsu, Pao-Yang Chen, Cheng-Fu Kao
Heterochromatin is a heritable form of gene repression, with critical roles in development and cell identity. Understanding how chromatin factors results in such repression is a fundamental question. Chromatin is assembled and disassembled during transcription, replication and repair by anti-silencing function 1 (Asf1), a highly conserved histone chaperone. Transcription and DNA replication are also affected by histone modifications that modify nucleosome dynamics, such as H2B ubiquitylation (H2Bub). We report here that H2Bub and Asf1 cooperatively promote transcriptional silencing at yeast telomeres and mating loci...
May 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28392790/hist1h1c-regulates-interferon-%C3%AE-and-inhibits-influenza-virus-replication-by-interacting-with-irf3
#6
Xiaokun Liu, Cha Yang, Yong Hu, Erming Lei, Xian Lin, Lianzhong Zhao, Zhong Zou, Anding Zhang, Hongbo Zhou, Huanchun Chen, Ping Qian, Meilin Jin
Influenza virus NS2 is well known for its role in viral ribonucleoprotein nuclear export; however, its function has not been fully understood. A recent study showed that NS2 might interact with HIST1H1C (H1C, H1.2). Histones have been found to affect influenza virus replication, such as the H2A, H2B, H3, and H4, but H1 has not been detected. Here, we found that H1C interacts with NS2 via its C-terminal in the nucleus and that H1C affects influenza virus replication. The H1N1 influenza virus replicates better in H1C knockout A549 cells compared to wild-type A549 cells, primarily because of the regulation of H1C on interferon-β (IFN-β)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28352541/incorporation-of-a-tag-helps-to-overcome-expression-variability-in-a-recombinant-host
#7
Saikat Bhattacharya, Divya Reddy, Raja Reddy, Asmita Sharda, Kakoli Bose, Sanjay Gupta
Epigenetics have witnessed a renewed interest over the past decade and assays with recombinant histones has become an important tool for uncovering various aspects of histone biology. However, at times absence of recombinant histone accumulation in bacteria is encountered which is also commonly observed for many eukaryotic proteins in general. In this study, we have investigated the effect of multiple parameters on heterologous expression of proteins. We show that there is marked variability in the accumulation of H2A...
September 2016: Biotechnology Reports
https://www.readbyqxmd.com/read/28257856/the-role-of-global-histone-post-translational-modifications-during-mammalian-hibernation
#8
Shannon N Tessier, Bryan E Luu, Jeffrey C Smith, Kenneth B Storey
Mammalian hibernators must cope with hypothermia, ischemia-reperfusion, and finite fuel reserves during days or weeks of continuous torpor. One means of lowering ATP demands during hibernation involves substantial transcriptional controls. The present research analyzed epigenetic regulatory factors as a means of achieving transcriptional control over cycles of torpor-arousal. This study analyzes differential regulation of select histone modifications (e.g. phosphorylation, acetylation, methylation), and identifies post-translational modifications on purified histones using mass spectrometry from thirteen-lined ground squirrels (Ictidomys tridecemlineatus)...
April 2017: Cryobiology
https://www.readbyqxmd.com/read/28235947/human-centromeric-cenp-a-chromatin-is-a-homotypic-octameric-nucleosome-at-all-cell-cycle-points
#9
Yael Nechemia-Arbely, Daniele Fachinetti, Karen H Miga, Nikolina Sekulic, Gautam V Soni, Dong Hyun Kim, Adeline K Wong, Ah Young Lee, Kristen Nguyen, Cees Dekker, Bing Ren, Ben E Black, Don W Cleveland
Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28209164/rnf40-regulates-gene-expression-in-an-epigenetic-context-dependent-manner
#10
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
#11
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/28178526/crl4-dcaf8-ubiquitin-ligase-targets-histone-h3k79-and-promotes-h3k9-methylation-in-the-liver
#12
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/28108335/tryptase-catalyzed-core-histone-truncation-a%C3%A2-novel-epigenetic-regulatory-mechanism-in-mast-cells
#13
Fabio R Melo, Ola Wallerman, Aida Paivandy, Gabriela Calounova, Ann-Marie Gustafson, Benjamin R Sabari, Giuliano Zabucchi, C David Allis, Gunnar Pejler
BACKGROUND: Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study, we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends. OBJECTIVE: Considering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells...
January 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27993980/genetic-mosaics-and-time-lapse-imaging-identify-functions-of-histone-h3-3-residues-in-mouse-oocytes-and-embryos
#14
Liquan Zhou, Boris Baibakov, Bertram Canagarajah, Bo Xiong, Jurrien Dean
During development from oocyte to embryo, genetic programs in mouse germ cells are reshaped by chromatin remodeling to orchestrate the onset of development. Epigenetic modifications of specific amino acid residues of core histones and their isoforms can dramatically alter activation and suppression of gene expression. H3.3 is a histone H3 variant that plays essential roles in mouse oocytes and early embryos, but the functional role of individual amino acid residues has been unclear because of technical hurdles...
February 1, 2017: Development
https://www.readbyqxmd.com/read/27935863/a-ruthenium-anticancer-compound-interacts-with-histones-and-impacts-differently-on-epigenetic-and-death-pathways-compared-to-cisplatin
#15
Cynthia Licona, Marie-Elodie Spaety, Antonelle Capuozzo, Moussa Ali, Rita Santamaria, Olivier Armant, Francois Delalande, Alain Van Dorsselaer, Sarah Cianferani, John Spencer, Michel Pfeffer, Georg Mellitzer, Christian Gaiddon
Ruthenium complexes are considered as potential replacements for platinum compounds in oncotherapy. Their clinical development is handicapped by a lack of consensus on their mode of action. In this study, we identify three histones (H3.1, H2A, H2B) as possible targets for an anticancer redox organoruthenium compound (RDC11). Using purified histones, we confirmed an interaction between the ruthenium complex and histones that impacted on histone complex formation. A comparative study of the ruthenium complex versus cisplatin showed differential epigenetic modifications on histone H3 that correlated with differential expression of histone deacetylase (HDAC) genes...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27926813/perturbation-of-h3k27me3-associated-epigenetic-processes-increases-agrobacterium-mediated-transformation
#16
Hidekazu Iwakawa, Benjamin C Carter, Brett C Bishop, Joe Ogas, Stanton B Gelvin
Agrobacterium-mediated transformation is a core technology for basic plant science and agricultural biotechnology. Improving transformation frequency is a major goal for plant transgenesis. We previously showed that T-DNA insertions in some histone genes decreased transformation susceptibility, whereas overexpression of several Arabidopsis H2A and H4 isoforms increased transformation. Overexpression of several histone H2B and H3 isoforms had little effect on transformation frequency. However, overexpression of histone H3-11 (HTR11) enhanced transformation...
January 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/27922451/direct-screening-for-chromatin-status-on-dna-barcodes-in-yeast-delineates-the-regulome-of-h3k79-methylation-by-dot1
#17
Hanneke Vlaming, Thom M Molenaar, Tibor van Welsem, Deepani W Poramba-Liyanage, Desiree E Smith, Arno Velds, Liesbeth Hoekman, Tessy Korthout, Sjoerd Hendriks, A F 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/27890612/in%C3%A2-vitro-reconstitution-and-biochemical-analyses-of-the-schizosaccharomyces-pombe-nucleosome
#18
Masako Koyama, Wataru Nagakura, Hiroki Tanaka, Tomoya Kujirai, Yuji Chikashige, Tokuko Haraguchi, Yasushi Hiraoka, Hitoshi Kurumizaka
Schizosaccharomyces pombe, which has a small genome but shares many physiological functions with higher eukaryotes, is a useful single-cell, model eukaryotic organism. In particular, many features concerning chromatin structure and dynamics, including heterochromatin, centromeres, telomeres, and DNA replication origins, are well conserved between S. pombe and higher eukaryotes. However, the S. pombe nucleosome, the fundamental structural unit of chromatin, has not been reconstituted in vitro. In the present study, we established the method to purify S...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27832544/in-vitro-assay-to-study-histone-ubiquitination-during-transcriptional-regulation
#19
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/27825936/new-insights-into-the-molecular-mechanisms-of-chemical-carcinogenesis-in-vivo-adduction-of-histone-h2b-by-a-reactive-metabolite-of-the-chemical-carcinogen-furan
#20
João Nunes, Inês L Martins, Catarina Charneira, Igor P Pogribny, Aline de Conti, Frederick A Beland, M Matilde Marques, Cristina C Jacob, Alexandra M M Antunes
Furan is a rodent hepatocarcinogen ubiquitously found in the environment and heat-processed foods. Furan undergoes cytochrome P450 2E1-catalyzed bioactivation to cis-2-butene-1,4-dial (BDA), which has been shown to form an electrophilic conjugate (GSH-BDA) with glutathione. Both BDA and GSH-BDA yield covalent adducts with lysine residues in proteins. Dose- and time-dependent epigenetic histone alterations have been observed in furan-treated rats. While the covalent modification of histones by chemical carcinogens has long been proposed, histone-carcinogen adducts have eluded detection in vivo...
December 15, 2016: Toxicology Letters
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