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https://www.readbyqxmd.com/read/28813589/regulation-of-stability-on-histone-h2a-h2b-dimer-by-h2a-tyr57-phosphorylation
#1
Takuma Sueoka, Gosuke Hayashi, Akimitsu Okamoto
Histone H2A and H2B form a H2A-H2B heterodimer, which is a fundamental unit of nucleosome assembly and disassembly. Several posttranslational modifications change the interface between the H2A-H2B dimer and the H3-H4 tetramer, and regulate nucleosome stability. However, posttranslational modifications associated with the interface between H2A and H2B have not been discussed. In this paper, it is shown that Tyr57 phosphorylation in H2A strongly influences H2A-H2B dimerization. Tyr57-phosphorylated H2A was chemically synthesized and utilized to reconstitute the H2A-H2B dimer and nucleosome as well as canonical H2A...
August 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28810797/asymmetric-breathing-motions-of-nucleosomal-dna-and-the-role-of-histone-tails
#2
Kaushik Chakraborty, Sharon M Loverde
The most important packing unit of DNA in the eukaryotic cell is the nucleosome. It undergoes large-scale structural re-arrangements during different cell cycles. For example, the disassembly of the nucleosome is one of the key steps for DNA replication, whereas reassembly occurs after replication. Thus, conformational dynamics of the nucleosome is crucial for different DNA metabolic processes. We perform three different sets of atomistic molecular dynamics simulations of the nucleosome core particle at varying degrees of salt conditions for a total of 0...
August 14, 2017: Journal of Chemical Physics
https://www.readbyqxmd.com/read/28806522/development-of-a-recombinant-multifunctional-biomacromolecule-for-targeted-gene-transfer-to-prostate-cancer-cells
#3
Arash Hatefi, Zahra Karjoo, Alireza Nomani
The objective of this study was to genetically engineer a fully functional single chain fusion peptide composed of motifs from diverse biological and synthetic origins that can perform multiple tasks including DNA condensation, cell targeting, cell transfection, particle shielding from immune system and effective gene transfer to prostate tumors. To achieve the objective, a single chain biomacromolecule (vector) consisted of four repetative units of histone H2A peptide, fusogenic peptide GALA, short elastin-like peptide and PC-3 cell targeting peptide was designed...
August 14, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28803373/th2a-is-phosphorylated-at-meiotic-centromere-by-haspin
#4
Masashi Hada, Jihye Kim, Erina Inoue, Yuko Fukuda, Hiromitsu Tanaka, Yoshinori Watanabe, Yuki Okada
Histone phosphorylation is sometimes associated with mitosis and meiosis. We have recently identified a phosphorylation of the 127th threonine on TH2A (pTH2A), a germ cell-specific H2A variant, in condensed spermatids and mitotic early preimplantation embryos of mice. Here, we further report the existence of pTH2A at the centromeres in metaphase I spermatocytes and oocytes. Moreover, we identified Haspin, a known kinase for the 3rd threonine on H3, is responsible for pTH2A in vivo. In contrast to the severe meiotic defect in oocytes treated with a Haspin inhibitor, pTH2A-deficient mice, in which the 127th threonine was replaced by alanine, maintained the fertility and exhibited no obvious defect in both oocytes and spermatogenesis...
August 12, 2017: Chromosoma
https://www.readbyqxmd.com/read/28790852/impact-of-combined-treatment-with-nimesulide-and-cisplatin-on-oral-carcinoma-cells
#5
Aleksandra Barac, Goran Mitulovic, Seth Hallström, Sonja Zehetmayer, Matthaeus Ch Grasl, Boban M Erovic
BACKGROUND: Despite significant advances in diagnosis and therapy, the rate of survival of patients with oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. AIM: This study aimed to identify molecular mechanisms of cell death of oral cancer cells caused by treatment with a nonselective Cox-2 inhibitor in combination with a low-dose chemotherapeutic drug. METHODS: Squamous cell carcinoma (SCC) cells SCC9 and SCC25 were subjected to mono- and combination therapy with nimesulide and cisplatin...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28790150/phosphorylation-of-histone-h2a-at-serine-95-a-plant-specific-mark-involved-in-flowering-time-regulation-and-h2a-z-deposition
#6
Yanhua Su, Shiliang Wang, Fei Zhang, Han Zheng, Yana Liu, Tongtong Huang, Yong Ding
Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter...
August 8, 2017: Plant Cell
https://www.readbyqxmd.com/read/28771339/specific-acetylation-patterns-of-h2a-z-form-transient-interactions-with-the-bptf-bromodomain
#7
Gabriella T Perell, Neeraj K Mishra, Babu Sudhamalla, Peter D Ycas, Kabirul Islam, William C K Pomerantz
Post-translational lysine acetylation of histone tails affect both chromatin accessibility and recruitment of multi-functional bromodomain-containing proteins for modulating transcription. Bromodomain and PHD finger-containing protein (BPTF) regulates transcription, but has also been implicated with high gene expression levels in a variety of cancers. In this report, the histone variant H2A.Z, which replaces H2A in chromatin, is evaluated for affinity towards BPTF with a specific recognition pattern of acetylated lysine residues of the N-terminal tail region...
August 3, 2017: Biochemistry
https://www.readbyqxmd.com/read/28746399/coordination-of-matrix-attachment-and-atp-dependent-chromatin-remodeling-regulate-auxin-biosynthesis-and-arabidopsis-hypocotyl-elongation
#8
Kyounghee Lee, Pil Joon Seo
Hypocotyl elongation is extensively controlled by hormone signaling networks. In particular, auxin metabolism and signaling play key roles in light-dependent hypocotyl growth. The nuclear matrix facilitates organization of DNA within the nucleus, and dynamic interactions between nuclear matrix and DNA are related to gene regulation. Conserved scaffold/matrix attachment regions (S/MARs) are anchored to the nuclear matrix by the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED (AHL) proteins in Arabidopsis. Here, we found that ESCAROLA (ESC)/AHL27 and SUPPRESSOR OF PHYTOCHROME B-4 #3 (SOB3)/AHL29 redundantly regulate auxin biosynthesis in the control of hypocotyl elongation...
2017: PloS One
https://www.readbyqxmd.com/read/28730681/histone-variants-expression-in-peripheral-blood-mononuclear-cells-of-patients-with-rheumatoid-arthritis
#9
Maryam Asadipour, Vahideh Hassan-Zadeh, Naheed Aryaeian, Farhad Shahram, Mahdi Mahmoudi
AIM: The purpose of the present study was to analyze the expression of four histone variants, implicated in the regulation of gene expression, in peripheral blood mononuclear cell (PBMC) samples of patients with rheumatoid arthritis and healthy controls. METHOD: We analyzed the expression of three genes encoding histone variants H3.3, H2A.Z, macroH2A1.1 and macroH2A1.2 in PBMC samples of 50 patients with RA, diagnosed according to American College of Rheumatology (ACR) criteria, and 51 matched healthy controls using SYBR green real-time polymerase chain reaction...
July 21, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28720323/rapid-divergence-of-histones-in-hydrozoa-cnidaria-and-evolution-of-a-novel-histone-involved-in-dna-damage-response-in-hydra
#10
Puli Chandramouli Reddy, Suyog Ubhe, Neha Sirwani, Rasika Lohokare, Sanjeev Galande
Histones are fundamental components of chromatin in all eukaryotes. Hydra, an emerging model system belonging to the basal metazoan phylum Cnidaria, provides an ideal platform to understand the evolution of core histone components at the base of eumetazoan phyla. Hydra exhibits peculiar properties such as tremendous regenerative capacity, lack of organismal senescence and rarity of malignancy. In light of the role of histone modifications and histone variants in these processes it is important to understand the nature of histones themselves and their variants in hydra...
June 15, 2017: Zoology: Analysis of Complex Systems, ZACS
https://www.readbyqxmd.com/read/28714954/c9orf72-expansion-disrupts-atm-mediated-chromosomal-break-repair
#11
Callum Walker, Saul Herranz-Martin, Evangelia Karyka, Chunyan Liao, Katherine Lewis, Waheba Elsayed, Vera Lukashchuk, Shih-Chieh Chiang, Swagat Ray, Padraig J Mulcahy, Mateusz Jurga, Ioannis Tsagakis, Tommaso Iannitti, Jayanth Chandran, Ian Coldicott, Kurt J De Vos, Mohamed K Hassan, Adrian Higginbottom, Pamela J Shaw, Guillaume M Hautbergue, Mimoun Azzouz, Sherif F El-Khamisy
Hexanucleotide repeat expansions represent the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, though the mechanisms by which such expansions cause neurodegeneration are poorly understood. We report elevated levels of DNA-RNA hybrids (R-loops) and double strand breaks in rat neurons, human cells and C9orf72 ALS patient spinal cord tissues. Accumulation of endogenous DNA damage is concomitant with defective ATM-mediated DNA repair signaling and accumulation of protein-linked DNA breaks...
July 17, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28714949/aspartate-%C3%AE-hydroxylase-disrupts-mitochondrial-dna-stability-and-function-in-hepatocellular-carcinoma
#12
C Tang, Y Hou, H Wang, K Wang, H Xiang, X Wan, Y Xia, J Li, W Wei, S Xu, Z Lei, T M Pawlik, H Wang, M Wu, F Shen
The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression of aspartate β-hydroxylase (ASPH) in HCC tissues, which was associated with tumor invasiveness and a worse prognosis. Currently, we unexpectedly observed the presence of ASPH in purified mitochondrial protein fraction. In addition, immunostaining of both exogenously and endogenously expressed ASPH showed a colocalization with mitochondrial biomarkers...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#13
Carolina J Simoes da Silva, Sol Fereres, Rocío Simón, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28710758/express-%C3%AE-h2ax-immunocytochemical-detection-of-dna-damage
#14
Nate Hopp, Jodi Hagen, Birte Aggeler, Alexander E Kalyuzhny
DNA can be damaged by many environmental factors including chemical agents and ionizing radiation which induce the formation of DNA double-stranded breaks (DSBs). If DSBs are not repaired in a timely fashion this may cause the disruption of genome integrity, which can result in cancer development. Typically, DSBs are followed by phosphorylation of histone protein H2AX, a member of the H2A family. Immunocytochemical detection of phosphorylated H2AX (e.g., γ-H2AX) appears to be a useful technique for assessing DNA damage...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28701485/gt-rich-promoters-can-drive-rna-pol-ii-transcription-and-deposition-of-h2a-z-in-african-trypanosomes
#15
Carolin Wedel, Konrad U Förstner, Ramona Derr, T Nicolai Siegel
Genome-wide transcription studies are revealing an increasing number of "dispersed promoters" that, unlike "focused promoters", lack well-conserved sequence motifs and tight regulation. Dispersed promoters are nevertheless marked by well-defined chromatin structures, suggesting that specific sequence elements must exist in these unregulated promoters. Here, we have analyzed regions of transcription initiation in the eukaryotic parasite Trypanosoma brucei, in which RNA polymerase II transcription initiation occurs over broad regions without distinct promoter motifs and lacks regulation...
July 12, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28698284/breaching-peripheral-tolerance-promotes-the-production-of-hiv-1-neutralizing-antibodies
#16
Kristin M S Schroeder, Amanda Agazio, Pamela J Strauch, Sean T Jones, Scott B Thompson, Michael S Harper, Roberta Pelanda, Mario L Santiago, Raul M Torres
A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env...
August 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28694242/chromatin-stiffening-underlies-enhanced-locus-mobility-after-dna-damage-in-budding-yeast
#17
Sébastien Herbert, Alice Brion, Jean-Michel Arbona, Mickaël Lelek, Adeline Veillet, Benoît Lelandais, Jyotsana Parmar, Fabiola García Fernández, Etienne Almayrac, Yasmine Khalil, Eleonore Birgy, Emmanuelle Fabre, Christophe Zimmer
DNA double-strand breaks (DSBs) induce a cellular response that involves histone modifications and chromatin remodeling at the damaged site and increases chromosome dynamics both locally at the damaged site and globally in the nucleus. In parallel, it has become clear that the spatial organization and dynamics of chromosomes can be largely explained by the statistical properties of tethered, but randomly moving, polymer chains, characterized mainly by their rigidity and compaction. How these properties of chromatin are affected during DNA damage remains, however, unclear...
July 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28679862/mysm1-2a-dub-is-an-epigenetic-regulator-in-human-melanoma-and-contributes-to-tumor-cell-growth
#18
Christina Wilms, Carsten M Kroeger, Adelheid V Hainzl, Ishani Banik, Clara Bruno, Ioanna Krikki, Vida Farsam, Meinhard Wlaschek, Martina V Gatzka
Histone modifying enzymes, such as histone deacetylases (HDACs) and polycomb repressive complex (PRC) components, have been implicated in regulating tumor growth, epithelial-mesenchymal transition, tumor stem cell maintenance, or repression of tumor suppressor genes - and may be promising targets for combination therapies of melanoma and other cancers. According to recent findings, the histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53-axis in hematopoiesis and tissue differentiation in mice, in part by modulating DNA-damage responses in stem cell and progenitor compartments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28669576/histone-h2a-monoubiquitination-in-neurodevelopmental-disorders
#19
REVIEW
Anshika Srivastava, Brian McGrath, Stephanie L Bielas
Covalent histone modifications play an essential role in gene regulation and cellular specification required for multicellular organism development. Monoubiquitination of histone H2A (H2AUb1) is a reversible transcriptionally repressive mark. Exchange of histone H2A monoubiquitination and deubiquitination reflects the succession of transcriptional profiles during development required to produce cellular diversity from pluripotent cells. Germ-line pathogenic variants in components of the H2AUb1 regulatory axis are being identified as the genetic basis of congenital neurodevelopmental disorders...
June 29, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28655885/mir-15a-mir-16-down-regulates-bmi1-impacting-ub-h2a-mediated-dna-repair-and-breast-cancer-cell-sensitivity-to-doxorubicin
#20
Nibedita Patel, Koteswara Rao Garikapati, Raj K Pandita, Dharmender Kumar Singh, Tej K Pandita, Utpal Bhadra, Manika Pal Bhadra
The B-lymphoma Moloney murine leukemia virus insertion region-1 protein (BMI1) acts as an oncogene in various cancers, including breast cancer. Recent evidence suggests that BMI1 is rapidly recruited to sites of DNA double strand breaks where it facilitates histone H2A ubiquitination and DNA double strand break repair by homologous recombination. Here we show that miR-15a and miR-16 expression is decreased during the initial period after DNA damage where it would otherwise down-regulate BMI1, impairing DNA repair...
June 27, 2017: Scientific Reports
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