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Histone H4

Jürgen Dieker, Jo H Berden, Marinka Bakker, Jean-Paul Briand, Sylviane Muller, Reinhard Voll, Christopher Sjöwall, Martin Herrmann, Luuk B Hilbrands, Johan van der Vlag
Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of anti-chromatin/chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features...
2016: PloS One
Mohammad B Hossain, Rehnuma Shifat, David G Johnson, Mark T Bedford, Konrad R Gabrusiewicz, Nahir Cortes-Santiago, Xuemei Luo, Zhimin Lu, Ravesanker Ezhilarasan, Erik P Sulman, Hong Jiang, Shawn S C Li, Frederick F Lang, Jessica Tyler, Mien-Chie Hung, Juan Fueyo, Candelaria Gomez-Manzano
DNA repair pathways enable cancer cells to survive DNA damage induced after genotoxic therapies. Tyrosine kinase receptors (TKRs) have been reported as regulators of the DNA repair machinery. TIE2 is a TKR overexpressed in human gliomas at levels that correlate with the degree of increasing malignancy. Following ionizing radiation, TIE2 translocates to the nucleus, conferring cells with an enhanced nonhomologous end-joining mechanism of DNA repair that results in a radioresistant phenotype. Nuclear TIE2 binds to key components of DNA repair and phosphorylates H4 at tyrosine 51, which, in turn, is recognized by the proto-oncogene ABL1, indicating a role for nuclear TIE2 as a sensor for genotoxic stress by action as a histone modifier...
April 2016: Science Advances
Pradyut K Paul, Mary E Rabaglia, Chen-Yu Wang, Donald S Stapleton, Ning Leng, Christina Kendziorski, Peter W Lewis, Mark P Keller, Alan D Attie
Anti-silencing function 1 (ASF1) is a histone H3-H4 chaperone involved in DNA replication and repair, and transcriptional regulation. Here, we identify ASF1B, the mammalian paralog to ASF1, as a proliferation-inducing histone chaperone in human β-cells. Overexpression of ASF1B led to distinct transcriptional signatures consistent with increased cellular proliferation and reduced cellular death. Using multiple methods of monitoring proliferation and mitotic progression, we show that overexpression of ASF1B is sufficient to induce human β-cell proliferation...
October 18, 2016: Cell Cycle
Saeed Izadi, Ramu Anandakrishnan, Alexey V Onufriev
Molecular Dynamics (MD) simulations based on the implicit solvent generalized Born (GB) models can provide significant computational advantages over the traditional explicit solvent simulations. However, the standard GB becomes prohibitively expensive for all-atom simulations of large structures; the model scales poorly, ~n^2, with the number of solute atoms. Here we combine our recently developed Optimal Point Charge Approximation (OPCA) with the Hierarchical Charge Partitioning (HCP) approximation to present an ~n log n multi-scale, yet fully atomistic, GB model (GB-HCPO)...
October 17, 2016: Journal of Chemical Theory and Computation
Fernanda Peres da Silveira, Carla Basso, Wagner Raupp, Morgana Dalpiaz, Karine Bertoldi, Ionara Rodrigues Siqueira, Pedro Dal Lago, Maristela Padilha de Souza, Viviane Rostirola Elsner
Our aim was to compare the basal levels of plasma brain-derived neurotrophic factor (BDNF) and global histone H4 acetylation in peripheral blood mononuclear cells (PBMCs) of healthy amateur runners (EXE group) with sedentary individuals (SED group) as well as to investigate the acute effect of a running race on these markers in the EXE group. Five days before the race, all participants were submitted to a basal blood collection. On the race day, two blood samples were collected in the EXE group before the running started and immediately at the end...
October 14, 2016: Journal of Physiological Sciences: JPS
Wei-Sheng Chen, Wen-Jin Xu, Hua-Qiang Zhu, Lei Gao, Miao-Jun Lai, Fu-Qiang Zhang, Wen-Hua Zhou, Hui-Fen Liu
Histone acetylation and other modifications of the chromatin are important regulators of gene expression and may contribute to drug-induced behaviors and neuroplasticity. Inhibition of histone deacetylases (HDAC) activity results in the change of some drug-induced behaviors,however, relatively little is known about the effects of HDAC inhibitors on heroin-seeking behavior. In the present study, male rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 days, followed by 14 daily 2hours extinction session in the operant chamber...
October 11, 2016: Brain Research
Long Jin, Hai-Ying Zhu, Qing Guo, Xiao-Chen Li, Yu-Chen Zhang, Cheng-Du Cui, Wen-Xue Li, Zheng-Yun Cui, Xi-Jun Yin, Jin-Dan Kang
Cloning remains as an important technique to enhance the reconstitution and distribution of animal population with high-genetic merit. One of the major detrimental factors of this technique is the abnormal epigenetic modifications. MGCD0103 is known as a histone deacetylase inhibitor. In this study, we investigated the effect of MGCD0103 on the in vitro blastocyst formation rate in porcine somatic cell nuclear transferred (SCNT) embryos and expression in acetylation of the histone H3 lysine 9 and histone H4 lysine 12...
September 13, 2016: Theriogenology
Jisung Kim, Siyoung Lee, Bo-Ryoung Choi, Hee Yang, Youjin Hwang, Jung Han Yoon Park, Frank M LaFerla, Jung-Soo Han, Ki Won Lee, Jiyoung Kim
SCOPE: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. METHODS AND RESULTS: Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane...
October 13, 2016: Molecular Nutrition & Food Research
Jianing Zhong, Xianfeng Li, Wanshi Cai, Yan Wang, Shanshan Dong, Jie Yang, Jian'an Zhang, Nana Wu, Yuanyuan Li, Fengbiao Mao, Cheng Zeng, Jinyu Wu, Xingzhi Xu, Zhong Sheng Sun
The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through altering statue of DNA methylation. However, recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; yet, the detailed mechanisms underlying TET1's role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets and a series of in vitro biochemical studies in human cell lines...
October 12, 2016: Nucleic Acids Research
Juanmei Gao, Hangze Ruan, Xianjie Qi, Yi Tao, Xia Guo, Wanhua Shen
Radial glial cells (RGs) are one of the important progenitor cells that can differentiate into neurons or glia to form functional neural circuits in the developing central nervous system (CNS). Histone deacetylases (HDACs) has been associated with visual activity dependent changes in BrdU-positive progenitor cells in the developing brain. We previously have shown that HDAC1 is involved in the experience-dependent proliferation of RGs. However, it is less clear whether two other members of class I HDACs, HDAC2 and HDAC3, are involved in the regulation of radial glia proliferation...
2016: Frontiers in Cellular Neuroscience
Richard C Brewster, Georgina C Gavins, Barbara Günthardt, Sarah Farr, Kimberly M Webb, Philipp Voigt, Alison N Hulme
Rapid, site-selective modification of cysteine residues with chloromethyl-triazole derivatives generates pseudo-acyl sLys motifs, mimicking important post-translational modifications. Near-native biotinylation of peptide and protein substrates is shown to be site-selective and modified histone H4 retains functional activity.
October 6, 2016: Chemical Communications: Chem Comm
Kristin D Kernohan, Arran McBride, Yanwei Xi, Nicole Martin, Jeremy Schwartzentruber, David A Dyment, Jacek Majewski, Susan Blaser, Kym M Boycott, David Chitayat
Post translational protein modifications exponentially expand the functional complement of proteins encoded by the human genome. One such modification is the covalent addition of a methyl group to arginine or lysine residues, which is used to regulate a substantial proportion of the proteome. Arginine and lysine methylation are catalyzed by protein arginine methyltransferase (PRMTs) and protein lysine methyltransferase proteins (PKMTs), respectively; each methyltransferase has a specific set of target substrates...
October 8, 2016: Clinical Genetics
Filomena Panza, Maria Claudia Alcaro, Fiorella Petrelli, Francesca Angelotti, Federico Pratesi, Paolo Rovero, Paola Migliorini
BACKGROUND: The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae minicircles, complexed with histone peptides...
October 4, 2016: Arthritis Research & Therapy
Laxmi N Mishra, Sharon Pepenella, Ryan Rogge, Jeffrey C Hansen, Jeffrey J Hayes
The activation of a silent gene locus is thought to involve pioneering transcription factors that initiate changes in the local chromatin structure to increase promoter accessibility and binding of downstream effectors. To better understand the molecular requirements for the first steps of locus activation, we investigated whether acetylation of a single nucleosome is sufficient to alter DNA accessibility within a condensed 25-nucleosome array. We found that acetylation mimics within the histone H4 tail domain increased accessibility of the surrounding linker DNA, with the increased accessibility localized to the immediate vicinity of the modified nucleosome...
October 6, 2016: Scientific Reports
Xianfang Rong, Xiaodi Qiu, Yongxiang Jiang, Dan Li, Jie Xu, Yinglei Zhang, Yi Lu
Histone acetylation plays key roles in gene expression, but its effects on superoxide dismutase 1 (SOD1) expression in senile cataract remains unknown. To address this problem, the study was to investigate the influence of histone acetylation on SOD1 expression and its effects in the pathogenesis of senile cataract. Senile cataract was classified into three types-nuclear cataract (NC), cortical cataract (CC), and posterior subcapsular cataract (SC)-using the Lens Opacities Classification System III. In senile cataracts, SOD1 expression decreased significantly...
October 5, 2016: Scientific Reports
Le Chang, Shoji Takada
Histone tail acetylation is a key epigenetic marker that tends to open chromatin folding and activate transcription. Despite intensive studies, precise roles of individual lysine acetylation in chromatin folding have only been poorly understood. Here, we revealed structural dynamics of tri-nucleosomes with several histone tail acetylation states and analyzed histone tail interactions with DNA by performing molecular simulations at an unprecedentedly high resolution. We found versatile acetylation-dependent landscapes of tri-nucleosome...
October 4, 2016: Scientific Reports
Wallace H Liu, Sarah C Roemer, Yeyun Zhou, Zih-Jie Shen, Briana K Dennehey, Jeremy L Balsbaugh, Jennifer C Liddle, Travis Nemkov, Natalie G Ahn, Kirk C Hansen, Jessica K Tyler, Mair Ea Churchill
The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex...
September 30, 2016: ELife
Ciro Milite, Alessandra Feoli, Monica Viviano, Donatella Rescigno, Agostino Cianciulli, Amodio Luca Balzano, Antonello Mai, Sabrina Castellano, Gianluca Sbardella
SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase (KMT) that monomethylates lysine 20 of histone H4 (H4K20) in vivo. Lysine residues of non-histone proteins including proliferating cell nuclear antigen (PCNA) and p53 are also monomethylated. As a consequence, the methyltransferase activity of the enzyme is implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. This review aims to provide an overview of the roles of SETD8 in physiological and pathological pathways and to discuss the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases and cellular activity...
2016: Clinical Epigenetics
Chia-Kai Liu, Wen-Tzu Liao, Yu-Chi Chu, Chien-Hui Yang, Kuan-Hung Chen, Chih-Hsien Wu, Chung-Ren Lin
BACKGROUND:  Pulsed radiofrequency (PRF) treatment offers pain relief for patients suffering from chronic pain who do not respond well to conventional treatments. We tested whether PRF treatment attenuated complete Freund's adjuvant (CFA)-induced inflammatory pain. Epigenetic modification of potassium-chloride cotransporter 2 (KCC2) gene expression was examined to elucidate the potential contributing mechanism. METHODS:  Male Sprague-Dawley rats were injected with CFA into the plantar surface of the left hind paw to induce inflammation...
September 28, 2016: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
Ye Shu, Qinghua Hu, Hai Long, Christopher Chang, Qianjin Lu, Rong Xiao
Autoimmune diseases are characterized by aberrant immune responses against healthy cells and tissues. However, the exact mechanisms underlying the development of these conditions remain unknown. CD4+CD25+ regulatory T cells (Tregs) are a subset of mature T cells which have an important role in maintaining immune homeostasis and preventing autoimmune diseases. Forkhead box p3 (Foxp3), a member of the fork head transcription factor family, is recognized as a marker of CD4+CD25+ Tregs. The decreased number and/or function of CD4+CD25+ Tregs in peripheral blood and related tissues has been demonstrated in systemic lupus erythematosus, systemic sclerosis, and other autoimmune diseases, which are at least partially regulated by epigenetic mechanisms...
September 29, 2016: Clinical Reviews in Allergy & Immunology
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