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https://www.readbyqxmd.com/read/28100329/-protective-effect-of-histone-acetylation-against-cortical-injury-in-neonatal-rats
#1
Ji-Chong Huang, Ya-Fei Li, Feng-Yan Zhao, Yi Qu, De-Zhi Mu
OBJECTIVE: To investigate the protective effect of histone acetylation against hypoxic-ischemic cortical injury in neonatal rats. METHODS: A total of 90 neonatal rats aged 3 days were divided into three groups: sham-operation, cortical injury model, and sodium butyrate (a histone deacetylase inhibitor) treatment. The rats in the model and the sodium butyrate treatment groups were intraperitoneally injected with lipopolysaccharide (0.05 mg/kg), and then right common carotid artery ligation was performed 2 hours later and the rats were put in a hypoxic chamber (oxygen concentration 6...
January 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28095649/the-effect-of-mechanical-stress-on-the-proliferation-adipogenic-differentiation-and-gene-expression-of-human-adipose-derived-stem-cells
#2
Nora E Paul, Bernd Denecke, Bong-Sung Kim, Alice Dreser, Jürgen Bernhagen, Norbert Pallua
To allow for a better implementation of external volume expansion to clinical applications for soft tissue regeneration, it is necessary to comprehensively understand the underlying mechanisms. Since human adipose-derived stem cells (hASCs) play a crucial role in soft tissue enlargement, we investigated the impact of cyclic stretch on gene expression, proliferation rate, and adipogenic differentiation of these cells. After cyclic stretching, RNA was extracted and subjected to DNA microarray analysis and RT-qPCR...
January 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#3
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077620/mitogen-induced-distinct-epi-alleles-are-phosphorylated-at-either-h3s10-or-h3s28-depending-on-h3k27-acetylation
#4
Dilshad H Khan, Shannon Healy, Shihua He, Daniel Lichtensztejn, Ludger Klewes, Kiran L Sharma, Veronica Lau, Sabine Mai, Geneviève P Delcuve, James R Davie
Stimulation of the MAPK pathway results in mitogen- and stress-activated protein kinase 1/2 (MSK1/2)-catalyzed phosphorylation of histone H3 at serine 10 or 28 and expression of immediate-early (IE) genes. In 10T1/2 mouse fibroblasts, phosphorylation of H3S10 and H3S28 occurs on different H3 molecules and in different nuclear regions. Likewise, we show that mitogen-induced H3S10 and H3S28 phosphorylation occurs in separate pools in human primary fibroblasts. High-resolution imaging studies on both cell types have revealed that H3S10 and H3S28 phosphorylation events can be induced in a single cell but on different alleles, giving rise to H3S10ph and H3S28ph epi-alleles...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28072869/discovery-and-molecular-basis-of-a-diverse-set-of-polycomb-repressive-complex-2-inhibitors-recognition-by-eed
#5
Ling Li, Hailong Zhang, Man Zhang, Mengxi Zhao, Lijian Feng, Xiao Luo, Zhenting Gao, Ying Huang, Ophelia Ardayfio, Ji-Hu Zhang, Ying Lin, Hong Fan, Yuan Mi, Guobin Li, Lei Liu, Leying Feng, Fangjun Luo, Lin Teng, Wei Qi, Johannes Ottl, Andreas Lingel, Dirksen E Bussiere, Zhengtian Yu, Peter Atadja, Chris Lu, En Li, Justin Gu, Kehao Zhao
Polycomb repressive complex 2 (PRC2), a histone H3 lysine 27 methyltransferase, plays a key role in gene regulation and is a known epigenetics drug target for cancer therapy. The WD40 domain-containing protein EED is the regulatory subunit of PRC2. It binds to the tri-methylated lysine 27 of the histone H3 (H3K27me3), and through which stimulates the activity of PRC2 allosterically. Recently, we disclosed a novel PRC2 inhibitor EED226 which binds to the K27me3-pocket on EED and showed strong antitumor activity in xenograft mice model...
2017: PloS One
https://www.readbyqxmd.com/read/28060183/gemcitabine-enhances-kras-mek-induced-matrix-metalloproteinase-10-expression-via-histone-acetylation-in-gemcitabine-resistant-pancreatic-tumor-initiating-cells
#6
Kazuya Shimizu, Takaaki Nishiyama, Yuichi Hori
OBJECTIVES: Advanced pancreatic ductal adenocarcinoma is resistant to systemic chemotherapy, resulting in a poor prognosis. We previously isolated a human pancreatic tumor-initiating cell line, KMC07, from a patient with acquired resistance to gemcitabine chemotherapy. To improve the anticancer effects of gemcitabine, we investigated the molecular mechanism of KMC07 cells' resistance to gemcitabine. METHODS: KMC07 cells were treated with gemcitabine, then gene expression and functional analyses performed using microarray, the quantitative polymerase chain reaction, immunoblotting, immunohistochemistry, chromatin immunoprecipitation, and cell transplantation into nude mice...
February 2017: Pancreas
https://www.readbyqxmd.com/read/28059702/cdk-regulated-dimerization-of-m18bp1-on-a-mis18-hexamer-is-necessary-for-cenp-a-loading
#7
Dongqing Pan, Kerstin Klare, Arsen Petrovic, Annika Take, Kai Walstein, Priyanka Singh, Arnaud Rondelet, Alex W Bird, Andrea Musacchio
Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A specific chaperone HJURP to centromeres and primes it for CENP-A loading...
January 6, 2017: ELife
https://www.readbyqxmd.com/read/28057758/down-regulation-of-claudin-2-expression-and-proliferation-by-epigenetic-inhibitors-in-human-lung-adenocarcinoma-a549-cells
#8
Asami Hichino, Miki Okamoto, Saeko Taga, Risa Akizuki, Satoshi Endo, Toshiyuki Matsunaga, Akira Ikari
Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases proliferation in adenocarcinoma cells. The chemicals which reduce claudin-2 expression may have anti-cancer effect, but such therapeutic medicines have not been developed. We found that azacitidine (AZA), a DNA methylation inhibitor, and trichostatin A (TSA) and sodium butyrate (NaB), histone deacetylase (HDAC) inhibitors, decrease claudin-2 levels. The effect of AZA was mediated by the inhibition of phosphorylated Akt and NFκB. LY-294002, an inhibitor of phosphatidyl inositol-3 kinase (PI3K), and BAY 11-7082, an NF-κB inhibitor, decreased claudin-2 levels...
January 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28049706/coordination-of-cell-cycle-progression-and-mitotic-spindle-assembly-involves-histone-h3-lysine-4-methylation-by-set1-compass
#9
Traude H Beilharz, Paul F Harrison, Douglas Maya Miles, Michael Ming See, Uyen Minh Merry Le, Ming Kalanon, Melissa Jane Curtis, Qambar Hasan, Julie Saksouk, Thanasis Margaritis, Frank Holstege, Vincent Geli, Bernhard Dichtl
Methylation of histone H3 lysine 4 (H3K4) by Set1 complex/COMPASS is a hallmark of eukaryotic chromatin, but it remains poorly understood how this post-translational modification contributes to the regulation of biological processes like the cell cycle. Here, we report a H3K4 methylation-dependent pathway in Saccharomyces cerevisiae that governs toxicity toward benomyl, a microtubule destabilizing drug. Benomyl-sensitive growth of wild-type cells required mono- and dimethylation of H3K4 and Pho23, a PHD-containing subunit of the Rpd3L complex...
January 2017: Genetics
https://www.readbyqxmd.com/read/28045428/butyrate-inhibits-cancerous-hct116-colon-cell-proliferation-but-to-a-lesser-extent-in-noncancerous-ncm460-colon-cells
#10
Huawei Zeng, David P Taussig, Wen-Hsing Cheng, LuAnn K Johnson, Reza Hakkak
Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects on colon cancer development. However, the mechanistic action of butyrate remains to be determined. We hypothesize that butyrate inhibits cancerous cell proliferation but to a lesser extent in noncancerous cells through regulating apoptosis and cellular-signaling pathways. We tested this hypothesis by exposing cancerous HCT116 or non-cancerous NCM460 colon cells to physiologically relevant doses of butyrate. Cellular responses to butyrate were characterized by Western analysis, fluorescent microscopy, acetylation, and DNA fragmentation analyses...
January 1, 2017: Nutrients
https://www.readbyqxmd.com/read/28042859/a-novel-role-of-silibinin-as-a-putative-epigenetic-modulator-in-human-prostate-carcinoma
#11
Ioannis Anestopoulos, Aristeidis P Sfakianos, Rodrigo Franco, Katerina Chlichlia, Mihalis I Panayiotidis, David J Kroll, Aglaia Pappa
Silibinin, extracted from milk thistle (Silybum marianum L.), has exhibited considerable preclinical activity against prostate carcinoma. Its antitumor and chemopreventive activities have been associated with diverse effects on cell cycle, apoptosis, and receptor-dependent mitogenic signaling pathways. Here we hypothesized that silibinin's pleiotropic effects may reflect its interference with epigenetic mechanisms in human prostate cancer cells. More specifically, we have demonstrated that silibinin reduces gene expression levels of the Polycomb Repressive Complex 2 (PRC2) members Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste Homolog 12 (SUZ12), and Embryonic Ectoderm Development (EED) in DU145 and PC3 human prostate cancer cells, as evidenced by Real Time Polymerase Chain Reaction (RT-PCR)...
December 31, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28038734/partially-assembled-nucleosome-structures-at%C3%A2-atomic-detail
#12
Georgy N Rychkov, Andrey V Ilatovskiy, Igor B Nazarov, Alexey V Shvetsov, Dmitry V Lebedev, Alexander Y Konev, Vladimir V Isaev-Ivanov, Alexey V Onufriev
The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation...
December 27, 2016: Biophysical Journal
https://www.readbyqxmd.com/read/28038453/histone-deacetylase-inhibitor-saha-mediates-mast-cell-death-and-epigenetic-silencing-of-constitutively-active-d816v-kit-in-systemic-mastocytosis
#13
Katarina Lyberg, Hani Abdulkadir Ali, Jennine Grootens, Matilda Kjellander, Malin Tirfing, Michel Arock, Hans Hägglund, Gunnar Nilsson, Johanna Ungerstedt
Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC...
December 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031332/regulator-of-g-protein-signaling-10-rgs10-expression-is-transcriptionally-silenced-in-activated-microglia-by-histone-deacetylase-activity
#14
Mohammed Alqinyah, Nagini Maganti, Mourad W Ali, Ruchi Yadav, Mei Gao, Han-Rong Weng, Susanna F Greer, Shelley B Hooks
RGS10 has emerged as a key regulator of pro-inflammatory cytokine production in microglia, functioning as an important neuroprotective factor. While RGS10 is normally expressed in microglia at high levels, expression is silenced in vitro following activation of TLR4 receptor. Given the ability of RGS10 to regulate inflammatory signaling, dynamic regulation of RGS10 levels in microglia may be an important mechanism to tune inflammatory responses. The goals of the current study were to confirm that RGS10 is suppressed in an in vivo inflammatory model of microglial activation and to determine the mechanism for activation-dependent silencing of Rgs10 expression in microglia...
December 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/28027934/histone-modifications-in-fasn-modulated-by-sterol-regulatory-element-binding-protein-1c-and-carbohydrate-responsive-element-binding-protein-under-insulin-stimulation-are-related-to-nafld
#15
Wei Shen, Xuan Du, Can Cai, Jialing Yao, Youping Zhou, Huihong Yu
Non-alcoholic fatty liver disease (NAFLD) and its causal factors of hepatic insulin resistance (IR) and type 2 diabetes are rapidly growing worldwide. Developing new therapeutic methods for these conditions requires a comprehensive understanding between hepatic lipid metabolism and IR. Sterol regulatory element-binding transcription factor 1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis...
December 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28024084/targeting-the-histone-methyltransferase-g9a-activates-imprinted-genes-and-improves-survival-of-a-mouse-model-of-prader-willi-syndrome
#16
Yuna Kim, Hyeong-Min Lee, Yan Xiong, Noah Sciaky, Samuel W Hulbert, Xinyu Cao, Jeffrey I Everitt, Jian Jin, Bryan L Roth, Yong-Hui Jiang
Prader-Willi syndrome (PWS) is an imprinting disorder caused by a deficiency of paternally expressed gene(s) in the 15q11-q13 chromosomal region. The regulation of imprinted gene expression in this region is coordinated by an imprinting center (PWS-IC). In individuals with PWS, genes responsible for PWS on the maternal chromosome are present, but repressed epigenetically, which provides an opportunity for the use of epigenetic therapy to restore expression from the maternal copies of PWS-associated genes. Through a high-content screen (HCS) of >9,000 small molecules, we discovered that UNC0638 and UNC0642-two selective inhibitors of euchromatic histone lysine N-methyltransferase-2 (EHMT2, also known as G9a)-activated the maternal (m) copy of candidate genes underlying PWS, including the SnoRNA cluster SNORD116, in cells from humans with PWS and also from a mouse model of PWS carrying a paternal (p) deletion from small nuclear ribonucleoprotein N (Snrpn (S)) to ubiquitin protein ligase E3A (Ube3a (U)) (mouse model referred to hereafter as m(+)/p(ΔS-U))...
December 26, 2016: Nature Medicine
https://www.readbyqxmd.com/read/28013028/h3k4-methyltransferase-activity-is-required-for-mll4-protein-stability
#17
Younghoon Jang, Chaochen Wang, Lenan Zhuang, Chengyu Liu, Kai Ge
Transcriptional enhancers play a key role in cell type-specific gene expression and cell fate transition. Enhancers are marked by histone H3K4 mono- and di-methylation (H3K4me1/2). The tumor suppressor MLL4 (KMT2D) is a major enhancer H3K4 mono- and di-methyltransferase with a partial functional redundancy with MLL3 (KMT2C). However, the functional role of MLL4 enzymatic activity remains elusive. To address this issue, we have generated MLL4 enzyme-dead knock-in (KI) embryonic stem (ES) cells and mice, which carry Y5477A/Y5523A/Y5563A mutations in the enzymatic SET domain of the MLL4 protein...
December 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28004105/uhrf2-decreases-h3k9ac-expression-by-interacting-with-it-through-the-phd-and-sra-ydg-domain-in-hepg2-hepatocellular-carcinoma-cells
#18
Ting Zhang, Linglin Zhao, Shengyuan Zeng, Lu Bai, Junxia Chen, Zheng Zhang, Yalan Wang, Changzhu Duan
Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is a multi-domain E3 ubiquitin ligase which is involved in epigenetic regulation and plays an essential role in tumorigenesis. However, the role of UHRF2 in histone H3 acetylation has not yet been fully elucidated and few studies have reported its role in hepatocellular carcinoma (HCC). In this study, we examined the correlation between UHRF2 and acetylated H3 in HCC. Immunohistochemistry and western blot analysis demonstrated that the levels of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 14 acetylation (H3K14ac) were higher in the HCC tissues and HepG2 HCC cells compared with the adjacent non-tumor tissues and L02 normal cells...
January 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27999197/effects-of-lipopolysaccharide-on-maturation-of-bovine-oocyte-in-vitro-and-its-possible-mechanisms
#19
Shan-Jiang Zhao, Yun-Wei Pang, Xue-Ming Zhao, Wei-Hua Du, Hai-Sheng Hao, Hua-Bin Zhu
Lipopolysaccharide disturbs the secretion of gonadotropin, endometrial function and implantation efficiency. However, there is little information regarding the effects of lipopolysaccharide on cyclic ovary activity, especially oocyte maturation. Therefore, we aimed to investigate the effects of lipopolysaccharide on the maturation potential of bovine oocytes. We found that lipopolysaccharide exposure significantly decreased the first polar body extrusion rate and delayed the cell cycle progression. The abnormal spindle rate was significantly increased in lipopolysaccharide treatment group, accompanied by disrupted localization and level of phosphorylated mitogen-activated protein kinase (p-MAPK)...
December 16, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999085/the-binding-specificity-of-phd-finger-domain-of-vin3-moderates-vernalization-response
#20
Donghawn Kim, Sibum Sung
Vernalization is a response to winter cold to initiate flowering in spring. VERNALIZATION INSENSITIVE 3 (VIN3) is induced by winter cold and is essential to vernalization response in Arabidopsis. VIN3 encodes a PHD-finger domain that binds to modified histones in vitro. An alteration in the binding specificity of the PHD-finger domain of VIN3 results in a hyper-vernalization response. The hyper-vernalization response is achieved by increased enrichments of VIN3 and tri-methylation of Histone H3 Lysine 27 at the FLC locus without invoking the increased enrichment of Polycomb Repressive Complex 2...
December 20, 2016: Plant Physiology
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