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https://www.readbyqxmd.com/read/29670118/global-h3-3-dynamic-deposition-defines-its-bimodal-role-in-cell-fate-transition
#1
Hai-Tong Fang, Chadi A El Farran, Qiao Rui Xing, Li-Feng Zhang, Hu Li, Bing Lim, Yuin-Han Loh
H3.3 is a histone variant, which is deposited on genebodies and regulatory elements, by Hira, marking active transcription. Moreover, H3.3 is deposited on heterochromatin by Atrx/Daxx complex. The exact role of H3.3 in cell fate transition remains elusive. Here, we investigate the dynamic changes in the deposition of the histone variant H3.3 during cellular reprogramming. H3.3 maintains the identities of the parental cells during reprogramming as its removal at early time-point enhances the efficiency of the process...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29670103/histone-h2ax-deficiency-causes-neurobehavioral-deficits-and-impaired-redox-homeostasis
#2
Urbain Weyemi, Bindu D Paul, Adele M Snowman, Parthav Jailwala, Andre Nussenzweig, William M Bonner, Solomon H Snyder
ATM drives DNA repair by phosphorylating the histone variant H2AX. While ATM mutations elicit prominent neurobehavioral phenotypes, neural roles for H2AX have been elusive. We report impaired motor learning and balance in H2AX-deficient mice. Mitigation of reactive oxygen species (ROS) with N-acetylcysteine (NAC) reverses the behavioral deficits. Mouse embryonic fibroblasts deficient for H2AX exhibit increased ROS production and failure to activate the antioxidant response pathway controlled by the transcription factor NRF2...
April 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29669917/ribosomal-dna-copy-loss-and-repeat-instability-in-atrx-mutated-cancers
#3
Maheshi Udugama, Elaine Sanij, Hsiao P J Voon, Jinbae Son, Linda Hii, Jeremy D Henson, F Lyn Chan, Fiona T M Chang, Yumei Liu, Richard B Pearson, Paul Kalitsis, Jeffrey R Mann, Philippe Collas, Ross D Hannan, Lee H Wong
ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors...
April 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29643413/nucleosomes-of-polyploid-trophoblast-giant-cells-mostly-consist-of-histone-variants-and-form-a-loose-chromatin-structure
#4
Koji Hayakawa, Kanae Terada, Tomohiro Takahashi, Hidehiro Oana, Masao Washizu, Satoshi Tanaka
Trophoblast giant cells (TGCs) are one of the cell types that form the placenta and play multiple essential roles in maintaining pregnancy in rodents. TGCs have large, polyploid nuclei resulting from endoreduplication. While previous studies have shown distinct gene expression profiles of TGCs, their chromatin structure remains largely unknown. An appropriate combination of canonical and non-canonical histones, also known as histone variants, allows each cell to exert its cell type-specific functions. Here, we aimed to reveal the dynamics of histone usage and chromatin structure during the differentiation of trophoblast stem cells (TSCs) into TGCs...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29643390/functional-crosstalk-between-histone-h2b-ubiquitylation-and-h2a-modifications-and-variants
#5
Felix Wojcik, Geoffrey P Dann, Leslie Y Beh, Galia T Debelouchina, Raphael Hofmann, Tom W Muir
Ubiquitylation of histone H2B at lysine residue 120 (H2BK120ub) is a prominent histone posttranslational modification (PTM) associated with the actively transcribed genome. Although H2BK120ub triggers several critical downstream histone modification pathways and changes in chromatin structure, less is known about the regulation of the ubiquitylation reaction itself, in particular with respect to the modification status of the chromatin substrate. Here we employ an unbiased library screening approach to profile the impact of pre-existing chromatin modifications on de novo ubiquitylation of H2BK120 by the cognate human E2:E3 ligase pair, UBE2A:RNF20/40...
April 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29643389/histone-h3-3-sub-variant-h3mm7-is-required-for-normal-skeletal-muscle-regeneration
#6
Akihito Harada, Kazumitsu Maehara, Yusuke Ono, Hiroyuki Taguchi, Kiyoshi Yoshioka, Yasuo Kitajima, Yan Xie, Yuko Sato, Takeshi Iwasaki, Jumpei Nogami, Seiji Okada, Tetsuro Komatsu, Yuichiro Semba, Tatsuya Takemoto, Hiroshi Kimura, Hitoshi Kurumizaka, Yasuyuki Ohkawa
Regulation of gene expression requires selective incorporation of histone H3 variant H3.3 into chromatin. Histone H3.3 has several subsidiary variants but their functions are unclear. Here we characterize the function of histone H3.3 sub-variant, H3mm7, which is expressed in skeletal muscle satellite cells. H3mm7 knockout mice demonstrate an essential role of H3mm7 in skeletal muscle regeneration. Chromatin analysis reveals that H3mm7 facilitates transcription by forming an open chromatin structure around promoter regions including those of myogenic genes...
April 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29629950/a-survey-of-somatic-mutations-in-41-genes-in-a-cohort-of-t-cell-lymphomas-identifies-frequent-mutations-in-genes-involved-in-epigenetic-modification
#7
Sebastian Fernandez-Pol, Lisa Ma, Rohan P Joshi, Daniel A Arber
Here, we utilize a high throughput sequencing panel that covers several genes known to be recurrently mutated in certain T-cell lymphoma subtypes as well as genes frequently mutated in other hematolymphoid malignancies, including myeloid neoplasms. This panel was applied to formalin-fixed, paraffin-embedded tissue from 84 biopsies from 78 patients selected for this study. The biopsies included ones a with a diagnosis of T-cell lymphoma (n=79), including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n=26) and angioimmunoblastic T-cell lymphoma (AITL; n=13), as well as 5 cases of atypical T-cell proliferations...
April 7, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29626011/centromere-transcription-allows-cenp-a-to-transit-from-chromatin-association-to-stable-incorporation
#8
Georg O M Bobkov, Nick Gilbert, Patrick Heun
Centromeres are essential for chromosome segregation and are specified epigenetically by the presence of the histone H3 variant CENP-A. In flies and humans, replenishment of the centromeric mark is uncoupled from DNA replication and requires the removal of H3 "placeholder" nucleosomes. Although transcription at centromeres has been previously linked to the loading of new CENP-A, the underlying molecular mechanism remains poorly understood. Here, we used Drosophila melanogaster tissue culture cells to show that centromeric presence of actively transcribing RNA polymerase II temporally coincides with de novo deposition of dCENP-A...
April 6, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29625540/the-role-of-transposable-elements-in-emergence-of-metazoa
#9
REVIEW
R N Mustafin, E K Khusnutdinova
Systems initially emerged for protecting genomes against insertions of transposable elements and represented by mechanisms of splicing regulation, RNA-interference, and epigenetic factors have played a key role in the evolution of animals. Many studies have shown inherited transpositions of mobile elements in embryogenesis and preservation of their activities in certain tissues of adult organisms. It was supposed that on the emergence of Metazoa the self-regulation mechanisms of transposons related with the gene networks controlling their activity could be involved in intercellular cell coordination in the cascade of successive divisions with differentiated gene expression for generation of tissues and organs...
March 2018: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/29622793/camp-independent-non-pigmentary-actions-of-variant-melanocortin-1-receptor-akt-mediated-activation-of-protective-responses-to-oxidative-dna-damage
#10
María Castejón-Griñán, Cecilia Herraiz, Conchi Olivares, Celia Jiménez-Cervantes, Jose Carlos García-Borrón
The melanocortin 1 receptor gene (MC1R), a well-established melanoma susceptibility gene, regulates the amount and type of melanin pigments formed within epidermal melanocytes. MC1R variants associated with increased melanoma risk promote the production of photosensitizing pheomelanins as opposed to photoprotective eumelanins. Wild-type (WT) MC1R activates DNA repair and antioxidant defenses in a cAMP-dependent fashion. Since melanoma-associated MC1R variants are hypomorphic in cAMP signaling, these non-pigmentary actions are thought to be defective in MC1R-variant human melanoma cells and epidermal melanocytes, consistent with a higher mutation load in MC1R-variant melanomas...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29616081/insertion-deletion-within-the-kdm6a-gene-is-significantly-associated-with-litter-size-in-goat
#11
Yang Cui, Hailong Yan, Ke Wang, Han Xu, Xuelian Zhang, Haijing Zhu, Jinwang Liu, Lei Qu, Xianyong Lan, Chuanying Pan
A previous whole-genome association analysis identified lysine demethylase 6A ( KDM6A ), which encodes a type of histone demethylase, as a candidate gene associated to goat fecundity. KDM6A gene knockout mouse disrupts gametophyte development, suggesting that it has a critical role in reproduction. In this study, goat KDM6A mRNA expression profiles were determined, insertion/deletion (indel) variants in the gene identified, indel variants effect on KDM6A gene expression assessed, and their association with first-born litter size analyzed in 2326 healthy female Shaanbei white cashmere goats...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29616066/modify-the-histone-to-win-the-battle-chromatin-dynamics-in-plant-pathogen-interactions
#12
REVIEW
Juan S Ramirez-Prado, Sophie J M Piquerez, Abdelhafid Bendahmane, Heribert Hirt, Cécile Raynaud, Moussa Benhamed
Relying on an immune system comes with a high energetic cost for plants. Defense responses in these organisms are therefore highly regulated and fine-tuned, permitting them to respond pertinently to the attack of a microbial pathogen. In recent years, the importance of the physical modification of chromatin, a highly organized structure composed of genomic DNA and its interacting proteins, has become evident in the research field of plant-pathogen interactions. Several processes, including DNA methylation, changes in histone density and variants, and various histone modifications, have been described as regulators of various developmental and defense responses...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29604400/arabidopsis-swc4-binds-dna-and-recruits-the-swr1-complex-to-modulate-histone-h2a-z-deposition-at-key-regulatory-genes
#13
Ángeles Gómez-Zambrano, Pedro Crevillén, José M Franco-Zorrilla, Juan A López, Jordi Moreno-Romero, Pawel Roszak, Juan Santos-González, Silvia Jurado, Jesús Vázquez, Claudia Köhler, Roberto Solano, Manuel Piñeiro, José A Jarillo
Deposition of the H2A.Z histone variant by the SWR1 complex (SWR1-C) in regulatory regions of specific loci modulates transcription. Characterization of Arabidopsis thaliana mutations in homologs of the yeast SWR1-C has revealed a role for H2A.Z exchange in a variety of developmental processes; nevertheless, the exact composition of the plant SWR1-C and how it is recruited to target genes remains to be established. Here we show that SWC4, the Arabidopsis homolog of the yeast SANT domain protein Swc4/Eaf2, is a DNA-binding protein that interacts with SWR1-C subunits...
March 28, 2018: Molecular Plant
https://www.readbyqxmd.com/read/29594595/vaccine-strategies-in-gliomas
#14
REVIEW
Michael Platten, Lukas Bunse, Dennis Riehl, Theresa Bunse, Katharina Ochs, Wolfgang Wick
PURPOSE OF REVIEW: To discuss the current state of glioma vaccine development and highlight the challenges associated with clinical implementation of these approaches. RECENT FINDINGS: Vaccination strategies against gliomas have matured considerably during the past years, although proof-of efficacy from controlled clinical trials is still lacking. Advances in antigen discovery, including the definition of neoepitopes including epidermal growth factor receptor variant III (EGFRvIII), isocitrate dehydrogenase (IDH)1R132H and Histone (H)3...
March 28, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29589302/methods-for-in-vivo-functional-studies-of-chromatin-modifying-enzymes-in-early-steps-of-colon-carcinogenesis
#15
Martine Chevillard-Briet, Fabrice Escaffit
Since chromatin-modifying enzymes are involved in most processes needing to access the DNA fiber such as transcription, replication or DNA repair, their involvement in the regulation of gene expression in numerous physiopathological contexts is widely studied. Most of these enzymes are essential for cell growth and survival due to their pleiotropic roles and studying their impact in vivo on organ development or tissue physiopathology is challenging. In this chapter, we describe a chemically-mediated method to induce colorectal carcinogenesis that we have used to identify in vivo the role of two chromatin modifying enzymes belonging to the same multimolecular complex, the histone acetyltransferase Tip60 and the histone variant-incorporating ATPase p400...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29588404/the-typhoid-toxin-produced-by-the-nontyphoidal-salmonella-enterica-serotype-javiana-is-required-for-induction-of-a-dna-damage-response-in-vitro-and-systemic-spread-in-vivo
#16
Rachel A Miller, Michael I Betteken, Xiaodong Guo, Craig Altier, Gerald E Duhamel, Martin Wiedmann
The Salmonella cytolethal distending toxin (S-CDT), first described as the "typhoid toxin" in Salmonella enterica subsp. enterica serotype Typhi, induces DNA damage in eukaryotic cells. Recent studies have shown that more than 40 nontyphoidal Salmonella (NTS) serotypes carry genes that encode S-CDT, yet very little is known about the activity, function, and role of S-CDT in NTS. Here we show that deletion of genes encoding the binding subunit ( pltB ) and a bacteriophage muramidase predicted to play a role in toxin export ( ttsA ) does not abolish toxin activity in the S-CDT-positive NTS Salmonella enterica subsp...
March 27, 2018: MBio
https://www.readbyqxmd.com/read/29588169/the-adaptor-protein-eny2-is-a-component-of-the-deubiquitination-module-of-the-arabidopsis-saga-transcriptional-co-activator-complex-but-not-of-the-trex-2-complex
#17
Alexander Pfab, Astrid Bruckmann, Julian Nazet, Rainer Merkl, Klaus D Grasser
The conserved nuclear protein ENY2 (Sus1 in yeast) is involved in coupling transcription and mRNA export in yeast and metazoa, as it is a component both of the transcriptional co-activator complex SAGA and of the mRNA export complex TREX-2. Arabidopsis thaliana ENY2 is widely expressed in the plant and it localises to the nucleoplasm, but unlike its yeast/metazoan orthologues it is not enriched in the nuclear envelope. Affinity purification of ENY2 in combination with mass spectrometry revealed that it co-purified with SAGA components, but not with the nuclear pore-associated TREX-2...
March 24, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29580382/high-levels-of-histones-promote-whole-genome-duplications-and-trigger-a-swe1-wee1-dependent-phosphorylation-of-cdc28-cdk1
#18
Douglas Maya Miles, Xenia Peñate, Trinidad Sanmartín Olmo, Frederic Jourquin, Maria Cruz Muñoz Centeno, Manuel Mendoza, Marie-Noelle Simon, Sebastian Chavez, Vincent Geli
Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response...
March 27, 2018: ELife
https://www.readbyqxmd.com/read/29576542/histone-variant-h3-3-and-its-functions-in-reprogramming
#19
Xing-Wei Huang, Xiang-Rong Cheng, Nan Wang, Yu-Wei Zhang, Chen Liao, Lian-Hong Jin, Lei Lei
Histones are a class of evolutionarily conserved nuclear proteins. Histone octamer wrapped by DNA sequence forms the nucleosome, the basic building blocks of eukaryotic chromatin. The nucleosomes keep the DNA in a condensed state, maintain the integrity of the genome, and ensure proper DNA replication, transcription, recombination and repair. Nucleosomes can regulate the biological processes of the cell through a number of distinct post-translational modifications (PTMs) and turnovers of histone variants. Although the histone H3 variant H3...
March 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29569072/posttranslational-modifications-of-cenp-a-marks-of-distinction
#20
REVIEW
Shashank Srivastava, Daniel R Foltz
Centromeres are specialized chromosome domain that serve as the site for kinetochore assembly and microtubule attachment during cell division, to ensure proper segregation of chromosomes. In higher eukaryotes, the identity of active centromeres is marked by the presence of CENP-A (centromeric protein-A), a histone H3 variant. CENP-A forms a centromere-specific nucleosome that acts as a foundation for centromere assembly and function. The posttranslational modification (PTM) of histone proteins is a major mechanism regulating the function of chromatin...
March 22, 2018: Chromosoma
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