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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
#1
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
#2
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
#3
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
#4
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, 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...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28710758/express-%C3%AE-h2ax-immunocytochemical-detection-of-dna-damage
#5
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
#6
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
#7
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...
July 11, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28694242/chromatin-stiffening-underlies-enhanced-locus-mobility-after-dna-damage-in-budding-yeast
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28652056/oxidative-stress-contributes-to-hepatocyte-growth-factor-dependent-pro-senescence-activity-of-ovarian-cancer-cells
#12
Justyna Mikuła-Pietrasik, Paweł Uruski, Martyna Pakuła, Konstantin Maksin, Sebastian Szubert, Aldona Woźniak, Eryk Naumowicz, Dariusz Szpurek, Andrzej Tykarski, Krzysztof Książek
The cancer-promoting activity of senescent peritoneal mesothelial cells (HPMCs) has already been well evidenced both in vitro and in vivo. Here we sought to determine if ovarian cancer cells may activate senescence in HPMCs. The study showed that conditioned medium (CM) from ovarian cancer cells (OVCAR-3, SKOV-3, A2780) inhibited growth and promoted the development of senescence phenotype (increased SA-β-Gal, γ-H2A.X, 53BP1, and decreased Cx43) in HPMCs. An analysis of tumors isolated from the peritoneum of patients with ovarian cancer revealed an abundance of senescent HPMCs in proximity to cancerous tissue...
June 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28648778/dna-replication-is-required-for-circadian-clock-function-by-regulating-rhythmic-nucleosome-composition
#13
Xiao Liu, Yunkun Dang, Toru Matsu-Ura, Yubo He, Qun He, Christian I Hong, Yi Liu
Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter...
June 9, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28645917/multivalent-binding-of-pwwp2a-to-h2a-z-regulates-mitosis-and-neural-crest-differentiation
#14
Sebastian Pünzeler, Stephanie Link, Gabriele Wagner, Eva C Keilhauer, Nina Kronbeck, Ramona Mm Spitzer, Susanne Leidescher, Yolanda Markaki, Edith Mentele, Catherine Regnard, Katrin Schneider, Daisuke Takahashi, Masayuki Kusakabe, Chiara Vardabasso, Lisa M Zink, Tobias Straub, Emily Bernstein, Masahiko Harata, Heinrich Leonhardt, Matthias Mann, Ralph Aw Rupp, Sandra B Hake
Replacement of canonical histones with specialized histone variants promotes altering of chromatin structure and function. The essential histone variant H2A.Z affects various DNA-based processes via poorly understood mechanisms. Here, we determine the comprehensive interactome of H2A.Z and identify PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A is a functionally uncharacterized, vertebrate-specific protein that binds very tightly to chromatin through a concerted multivalent binding mode. Two internal protein regions mediate H2A...
June 23, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28626237/cd4-t-cells-memorize-obesity-and-promote-weight-regain
#15
Jianghuan Zou, Beibei Lai, Mingzhu Zheng, Qin Chen, Shujun Jiang, Anying Song, Zan Huang, Peiliang Shi, Xin Tu, Di Wang, Linrong Lu, Zhaoyu Lin, Xiang Gao
Body weight regain often causes failure of obesity therapies while the underlying mechanism remains largely unknown. In this study, we report that immune cells, especially CD4+ T cells, mediate the 'memory' of previous obese status. In a weight gain-loss-regain model, we found that C57BL/6J mice with an obesity history showed a much faster rate of body weight regain. This obesity memory could last for at least 2 months after previously obese mice were kept at the same body weight as non-obese mice. Surprisingly, such obesity memory was abrogated by dexamethasone treatment, whereas immunodeficient Rag1(-/-) and H2A(-/-) mice failed to establish such memory...
June 19, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28624371/histone-ubiquitination-in-the-dna-damage-response
#16
REVIEW
Michael Uckelmann, Titia K Sixma
DNA double strand breaks need to be repaired in an organized fashion to preserve genomic integrity. In the organization of faithful repair, histone ubiquitination plays a crucial role. Recent findings suggest an integrated model for DNA repair regulation through site-specific histone ubiquitination and crosstalk to other posttranslational modifications. Here we discuss how site-specific histone ubiquitination is achieved on a molecular level and how different multi-protein complexes work together to integrate different histone ubiquitination states...
June 9, 2017: DNA Repair
https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#17
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ~30%, while ~70% are aneuploid and senescent cells (AASCs), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28607146/epigenetic-transcriptional-memory-of-gal-genes-depends-on-growth-in-glucose-and-the-tup1-transcription-factor-in-saccharomyces-cerevisiae
#18
Varun Sood, Ivelisse Cajigas, Agustina D'Urso, William H Light, Jason H Brickner
Previously expressed inducible genes can remain poised for faster reactivation for multiple cell divisions, a conserved phenomenon called epigenetic transcriptional memory. The GAL genes in Saccharomyces cerevisiae show faster reactivation for up to seven generations after being repressed. During memory, previously produced Gal1 protein enhances the rate of reactivation of GAL1, GAL10, GAL2 and GAL7 These genes also interact with the nuclear pore complex (NPC) and localize to the nuclear periphery both when active and during memory...
June 12, 2017: Genetics
https://www.readbyqxmd.com/read/28604691/ino80-exchanges-h2a-z-for-h2a-by-translocating-on-dna-proximal-to-histone-dimers
#19
Sandipan Brahma, Maheshi I Udugama, Jongseong Kim, Arjan Hada, Saurabh K Bhardwaj, Solomon G Hailu, Tae-Hee Lee, Blaine Bartholomew
ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. These chromatin remodellers generally function by translocating along nucleosomal DNA at the H3-H4 interface of nucleosomes. Here we show that, unlike other remodellers, INO80 translocates along DNA at the H2A-H2B interface of nucleosomes and persistently displaces DNA from the surface of H2A-H2B. DNA translocation and DNA torsional strain created near the entry site of nucleosomes by INO80 promotes both the mobilization of nucleosomes and the selective exchange of H2A...
June 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28601068/prevalence-of-autoantibodies-against-3-dg-glycated-h2a-protein-in-type-2-diabetes
#20
J M Ashraf, S M S Abdullah, S Ahmad, S Fatma, M H Baig, J Iqbal, A M Madkhali, A B A Jerah
Advanced glycation end-products (AGEs) have been found to be critically involved in initiation or progression of diabetes secondary complications (nephropathy, retinopathy, neuropathy, and angiopathy). Various hyper-glycating carbonyl compounds such as 3-deoxyglucosone (3-DG) are produced in pathophysiological conditions that form AGEs in high quantity both in vivo and in vitro. In the first stage of this study, we glycated histone H2A protein by 3-DG, and the results showed the formation of various intermediates and AGEs as well as structural changes in the protein...
May 2017: Biochemistry. Biokhimii︠a︡
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