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Histone variants

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https://www.readbyqxmd.com/read/28937961/regulation-of-chromatin-assembly-and-cell-transformation-by-formaldehyde-exposure-in-human-cells
#1
Danqi Chen, Lei Fang, Shenglin Mei, Hongjie Li, Xia Xu, Thomas L Des Marais, Kun Lu, X Shirley Liu, Chunyuan Jin
BACKGROUND: Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies have shown that exogenous FA causes only a modest increase in DNA adduct formation compared with the amount of adducts formed by endogenous FA, raising the possibility that epigenetic mechanisms may contribute to FA-mediated carcinogenicity. OBJECTIVES: We investigated the effects of FA exposure on histone modifications and chromatin assembly. We also examined the role of defective chromatin assembly in FA-mediated transcription and cell transformation...
September 21, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28934504/accumulation-of-histone-variant-h3-3-with-age-is-associated-with-profound-changes-in-the-histone-methylation-landscape
#2
Andrey Tvardovskiy, Veit Schwämmle, Stefan J Kempf, Adelina Rogowska-Wrzesinska, Ole N Jensen
Deposition of replication-independent histone variant H3.3 into chromatin is essential for many biological processes, including development and reproduction. Unlike replication-dependent H3.1/2 isoforms, H3.3 is expressed throughout the cell cycle and becomes enriched in postmitotic cells with age. However, lifelong dynamics of H3 variant replacement and the impact of this process on chromatin organization remain largely undefined. Using quantitative middle-down proteomics we demonstrate that H3.3 accumulates to near saturation levels in the chromatin of various mouse somatic tissues by late adulthood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#3
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#4
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933623/the-defining-dna-methylation-signature-of-kabuki-syndrome-enables-functional-assessment-of-genetic-variants-of-unknown-clinical-significance
#5
Erfan Aref-Eshghi, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, David Rodenhiser, Charles Schwartz, Bekim Sadikovic
Kabuki syndrome (KS) is caused by mutations in KMT2D, which is a histone methyltransferase involved in methylation of H3K4, a histone marker associated with DNA methylation. Analysis of >450,000 CpGs in 24 KS patients with pathogenic mutations in KMT2D and 216 controls, identified several genomic regions, along with 1,504 CpG sites with significant DNA methylation changes including a number of Hox genes and the MYO1F gene. Using the most differentiating and significant probes and regions we developed a "methylation variant pathogenicity (MVP) score," which enables 100% sensitive and specific identification of individuals with KS, which was confirmed using multiple public and internal patient DNA methylation databases...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28928947/puzzles-in-modern-biology-v-why-are-genomes-overwired
#6
Steven A Frank
Many factors affect eukaryotic gene expression. Transcription factors, histone codes, DNA folding, and noncoding RNA modulate expression. Those factors interact in large, broadly connected regulatory control networks. An engineer following classical principles of control theory would design a simpler regulatory network. Why are genomes overwired? Neutrality or enhanced robustness may lead to the accumulation of additional factors that complicate network architecture. Dynamics progresses like a ratchet. New factors get added...
2017: F1000Research
https://www.readbyqxmd.com/read/28928274/the-ubiquitin-ligase-e3-psh1p-is-required-for-proper-segregation-of-both-centromeric-and-two-micron-plasmids-in-saccharomyces-cerevisiae
#7
Meredith B Metzger, Jessica L Scales, Mitchell F Dunklebarger, Allan M Weissman
Protein degradation by the ubiquitin-proteasome system is essential to many processes. We sought to assess its involvement in the turnover of mitochondrial proteins in Saccharomyces cerevisiae We find that deletion of a specific ubiquitin ligase (E3), Psh1p, increases the abundance of a temperature-sensitive mitochondrial protein, mia40-4pHA, when it is expressed from a centromeric plasmid. Deletion of Psh1p unexpectedly elevates the levels of other proteins expressed from centromeric plasmids. Loss of Psh1p does not increase the rate of turn-over of mia40-4pHA, affect total protein synthesis, or increase the protein levels of chromosomal genes...
September 19, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#8
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28913935/induction-of-cancer-cell-stemness-by-depletion-of-macrohistone-h2a1-in-hepatocellular-carcinoma
#9
Oriana Lo Re, Caterina Fusilli, Francesca Rappa, Matthias Van Haele, Julien Douet, Jana Pindjakova, Sura Wanessa Rocha, Illar Pata, Barbora Valčíková, Stjepan Uldrijan, Raymond S Yeung, Christina Alves Peixoto, Tania Roskams, Marcus Buschbeck, Tommaso Mazza, Manlio Vinciguerra
Hepatocellular carcinomas (HCC) contain a sub-population of cancer stem cells (CSCs), which exhibit stem-cell like features and are responsible for tumor relapse, metastasis, and chemoresistance. The development of effective treatments for HCC will depend on a molecular-level understanding of the specific pathways driving CSC emergence and stemness. MacroH2A1 is a variant of the histone H2A and an epigenetic regulator of stem cell function, where it promotes differentiation and, conversely, acts as a barrier to somatic cell reprogramming...
September 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28905131/exploring-evidence-of-positive-selection-signatures-in-cattle-breeds-selected-for-different-traits
#10
Mengistie Taye, Wonseok Lee, Soomin Jeon, Joon Yoon, Tadelle Dessie, Olivier Hanotte, Okeyo Ally Mwai, Stephen Kemp, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
Since domestication, the genome landscape of cattle has been changing due to natural and artificial selection forces resulting in several general and specialized cattle breeds of the world. Identifying genomic regions affected due to these forces in livestock gives an insight into the history of selection for economically important traits and genetic adaptation to specific environments of the populations under consideration. This study explores the genes/genomic regions under selection in relation to the phenotypes of Holstein, Hanwoo, and N'Dama cattle breeds using Tajima's D, XP-CLR, and XP-EHH population statistical methods...
September 13, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28904333/the-ino80-complex-mediates-epigenetic-centromere-propagation-via-active-removal-of-histone-h3
#11
Eun Shik Choi, Youngseo Cheon, Keunsoo Kang, Daeyoup Lee
The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-A(Cnp1) chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1(Hrp1)...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28899740/histone-3-3-mutations-in-giant-cell-tumor-and-giant-cell-rich-sarcomas-of-bone
#12
Alberto Righi, Irene Mancini, Marco Gambarotti, Piero Picci, Gabriella Gamberi, Cristina Marraccini, Angelo Paolo Dei Tos, Lisa Simi, Pamela Pinzani, Alessandro Franchi
Mutually exclusive histone 3.3 gene mutations have been recognized in chondroblastoma and giant cell tumor of bone (GCTB), which may be useful for differential diagnostic purposes in morphologically ambiguous cases. While over 90% of GCTB presents histone 3.3 variants exclusively in the H3F3A gene, chondroblastoma is mutated mainly in H3F3B. In this study we examined a series of giant cell rich primary bone tumors, aiming to evaluate the possible diagnostic role of histone 3.3 mutations in the differential diagnosis between GCTB and giant cell rich sarcomas...
September 9, 2017: Human Pathology
https://www.readbyqxmd.com/read/28898696/a-dual-role-of-caspase-8-in-triggering-and-sensing-proliferation-associated-dna-damage-a-key-determinant-of-liver-cancer-development
#13
Yannick Boege, Mohsen Malehmir, Marc E Healy, Kira Bettermann, Anna Lorentzen, Mihael Vucur, Akshay K Ahuja, Friederike Böhm, Joachim C Mertens, Yutaka Shimizu, Lukas Frick, Caroline Remouchamps, Karun Mutreja, Thilo Kähne, Devakumar Sundaravinayagam, Monika J Wolf, Hubert Rehrauer, Christiane Koppe, Tobias Speicher, Susagna Padrissa-Altés, Renaud Maire, Jörn M Schattenberg, Ju-Seong Jeong, Lei Liu, Stefan Zwirner, Regina Boger, Norbert Hüser, Roger J Davis, Beat Müllhaupt, Holger Moch, Henning Schulze-Bergkamen, Pierre-Alain Clavien, Sabine Werner, Lubor Borsig, Sanjiv A Luther, Philipp J Jost, Ricardo Weinlich, Kristian Unger, Axel Behrens, Laura Hillert, Christopher Dillon, Michela Di Virgilio, David Wallach, Emmanuel Dejardin, Lars Zender, Michael Naumann, Henning Walczak, Douglas R Green, Massimo Lopes, Inna Lavrik, Tom Luedde, Mathias Heikenwalder, Achim Weber
Concomitant hepatocyte apoptosis and regeneration is a hallmark of chronic liver diseases (CLDs) predisposing to hepatocellular carcinoma (HCC). Here, we mechanistically link caspase-8-dependent apoptosis to HCC development via proliferation- and replication-associated DNA damage. Proliferation-associated replication stress, DNA damage, and genetic instability are detectable in CLDs before any neoplastic changes occur. Accumulated levels of hepatocyte apoptosis determine and predict subsequent hepatocarcinogenesis...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28894165/evolution-analysis-of-heterogeneous-non-small-cell-lung-carcinoma-by-ultra-deep-sequencing-of-the-mitochondrial-genome
#14
Wafa Amer, Csaba Toth, Erik Vassella, Jeannine Meinrath, Ulrike Koitzsch, Anne Arens, Jia Huang, Hannah Eischeid, Alexander Adam, Reinhard Buettner, Andreas Scheel, Stephan C Schaefer, Margarete Odenthal
Accurate assessment of tumour heterogeneity is an important issue that influences prognosis and therapeutic decision in molecular pathology. Due to the shortage of protective histones and a limited DNA repair capacity, the mitochondrial (mt)-genome undergoes high variability during tumour development. Therefore, screening of mt-genome represents a useful molecular tool for assessing precise cell lineages and tracking tumour history. Here, we describe a highly specific and robust multiplex PCR-based ultra-deep sequencing technology for analysis of the whole mt-genome (wmt-seq) on low quality-DNA from formalin-fixed paraffin-embedded tissues...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883625/redundant-functions-for-nap1-and-chz1-in-h2a-z-deposition
#15
Raghuvar Dronamraju, Srinivas Ramachandran, Deepak K Jha, Alexander T Adams, Julia V DiFiore, Michael A Parra, Nikolay V Dokholyan, Brian D Strahl
H2A.Z is a histone H2A variant that contributes to transcriptional regulation, DNA damage response and limits heterochromatin spreading. In Saccharomyces cerevisiae, H2A.Z is deposited by the SWR-C complex, which relies on several histone chaperones including Nap1 and Chz1 to deliver H2A.Z-H2B dimers to SWR-C. However, the mechanisms by which Nap1 and Chz1 cooperate to bind H2A.Z and their contribution to H2A.Z deposition in chromatin is not well understood. Using structural modeling and molecular dynamics simulations, we identify a series of H2A...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28872116/chromatin-immunoprecipitation-chip-protocol-for-low-abundance-embryonic-samples
#16
Rizwan Rehimi, Michaela Bartusel, Francesca Solinas, Janine Altmüller, Alvaro Rada-Iglesias
Chromatin immunoprecipitation (ChIP) is a widely-used technique for mapping the localization of post-translationally modified histones, histone variants, transcription factors, or chromatin-modifying enzymes at a given locus or on a genome-wide scale. The combination of ChIP assays with next-generation sequencing (i.e., ChIP-Seq) is a powerful approach to globally uncover gene regulatory networks and to improve the functional annotation of genomes, especially of non-coding regulatory sequences. ChIP protocols normally require large amounts of cellular material, thus precluding the applicability of this method to investigating rare cell types or small tissue biopsies...
August 29, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28870212/chromosome-contacts-in-activated-t-cells-identify-autoimmune-disease-candidate-genes
#17
Oliver S Burren, Arcadio Rubio García, Biola-Maria Javierre, Daniel B Rainbow, Jonathan Cairns, Nicholas J Cooper, John J Lambourne, Ellen Schofield, Xaquin Castro Dopico, Ricardo C Ferreira, Richard Coulson, Frances Burden, Sophia P Rowlston, Kate Downes, Steven W Wingett, Mattia Frontini, Willem H Ouwehand, Peter Fraser, Mikhail Spivakov, John A Todd, Linda S Wicker, Antony J Cutler, Chris Wallace
BACKGROUND: Autoimmune disease-associated variants are preferentially found in regulatory regions in immune cells, particularly CD4(+) T cells. Linking such regulatory regions to gene promoters in disease-relevant cell contexts facilitates identification of candidate disease genes. RESULTS: Within 4 h, activation of CD4(+) T cells invokes changes in histone modifications and enhancer RNA transcription that correspond to altered expression of the interacting genes identified by promoter capture Hi-C...
September 4, 2017: Genome Biology
https://www.readbyqxmd.com/read/28869584/an-xqtl-map-integrates-the-genetic-architecture-of-the-human-brain-s-transcriptome-and-epigenome
#18
Bernard Ng, Charles C White, Hans-Ulrich Klein, Solveig K Sieberts, Cristin McCabe, Ellis Patrick, Jishu Xu, Lei Yu, Chris Gaiteri, David A Bennett, Sara Mostafavi, Philip L De Jager
We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci...
September 4, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28862252/genome-wide-identification-of-histone-h2a-and-histone-variant-h2a-z-interacting-proteins-by-bppi-seq
#19
Yi Zhang, Wai Lim Ku, Shuai Liu, Kairong Cui, Wenfei Jin, Qingsong Tang, William Lu, Bing Ni, Keji Zhao
H2A is a nucleosome core subunit involved in organizing DNA into a chromatin structure that is often inaccessible to regulatory enzymes. Replacement of H2A by its variant H2A.Z renders chromatin accessible at enhancers and promoters. However, it remains unclear how H2A.Z functions so differently from canonical H2A. Here we report the genome-wide identification of proteins that directly interact with H2A and H2A.Z in vivo using a novel strategy, bPPI-seq. We show that bPPI-seq is a sensitive and robust technique to identify protein-protein interactions in vivo...
September 1, 2017: Cell Research
https://www.readbyqxmd.com/read/28856239/histone-hypervariants-h2a-z-1-and-h2a-z-2-play-independent-and-context-specific-roles-in-neuronal-activity-induced-transcription-of-arc-arg3-1-and-other-immediate-early-genes
#20
Carissa J Dunn, Pushpita Sarkar, Emma R Bailey, Shannon Farris, Meilan Zhao, James M Ward, Serena M Dudek, Ramendra N Saha
The histone variant H2A.Z is an essential and conserved regulator of eukaryotic gene transcription. However, the exact role of this histone in the transcriptional process remains perplexing. In vertebrates, H2A.Z has two hypervariants, H2A.Z.1 and H2A.Z.2, that have almost identical sequences except for three amino acid residues. Due to such similarity, functional specificity of these hypervariants in neurobiological processes, if any, remain largely unknown. In this study with dissociated rat cortical neurons, we asked if H2A...
July 2017: ENeuro
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