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histone acetylation

Flor M Mendez, Felipe J Núñez, Rocío I Zorrilla-Veloz, Pedro R Lowenstein, Maria G Castro
Epigenetic modifications may be involved in the development and progression of glioma. Changes in methylation and acetylation of promoters and regulatory regions of oncogenes and tumor suppressors can lead to changes in gene expression and play an important role in the pathogenesis of brain tumors. Native chromatin immunoprecipitation (ChIP) is a popular technique that allows the detection of modifications or other proteins tightly bound to DNA. In contrast to cross-linked ChIP, in native ChIP, cells are not treated with formaldehyde to covalently link protein to DNA...
January 29, 2018: Journal of Visualized Experiments: JoVE
Deqing Sun, Aiying Xue, Xia Xue, Manru Ren, Jing Wu, Rongmei Wang
High mobility group box 1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic injury, initiates inflammatory response and aggravates brain tissue damage. Acetylpuerarin (AP), an acetylated derivative of puerarin, was reported to protect against cerebrovascular ischemia-reperfusion injury in rats through anti-inflammation. In the present study, we aim to investigate whether AP inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated BV2 microglia...
February 1, 2018: Die Pharmazie
Henel Sein, Kristina Reinmets, Kadri Peil, Kersti Kristjuhan, Signe Värv, Arnold Kristjuhan
Rpb9 is a non-essential subunit of RNA polymerase II that is involved in DNA transcription and repair. In budding yeast, deletion of RPB9 causes several phenotypes such as slow growth and temperature sensitivity. We found that simultaneous mutation of multiple N-terminal lysines within histone H3 was lethal in rpb9Δ cells. Our results indicate that hypoacetylation of H3 leads to inefficient repair of DNA double-strand breaks, while activation of the DNA damage checkpoint regulators γH2A and Rad53 is suppressed in Rpb9-deficient cells...
February 13, 2018: Scientific Reports
Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq)...
February 10, 2018: Free Radical Biology & Medicine
Mohi Ahmed, Andrea Streit
During development, multipotent progenitor cells must maintain their identity while retaining the competence to respond to new signalling cues that drive cell fate decisions. This depends on both DNA-bound transcription factors and surrounding histone modifications. Here we identify the histone demethylase Lsd1 as a crucial component of the molecular machinery that preserves progenitor identity in the developing ear prior to lineage commitment. While Lsd1 is mainly associated with repressive complexes, we show that in ear precursors it is required to maintain active transcription of otic genes...
February 5, 2018: Development
Chih-Chao Hsu, Jiejun Shi, Chao Yuan, Dan Zhao, Shiming Jiang, Jie Lyu, Xiaolu Wang, Haitao Li, Hong Wen, Wei Li, Xiaobing Shi
Histone acetylation is associated with active transcription in eukaryotic cells. It helps to open up the chromatin by neutralizing the positive charge of histone lysine residues and providing binding platforms for "reader" proteins. The bromodomain (BRD) has long been thought to be the sole protein module that recognizes acetylated histones. Recently, we identified the YEATS domain of AF9 (ALL1 fused gene from chromosome 9) as a novel acetyl-lysine-binding module and showed that the ENL (eleven-nineteen leukemia) YEATS domain is an essential acetyl-histone reader in acute myeloid leukemias...
January 1, 2018: Genes & Development
Jennifer W Israel, Grace A Chappell, Jeremy M Simon, Sebastian Pott, Alexias Safi, Lauren Lewis, Paul Cotney, Hala S Boulos, Wanda Bodnar, Jason D Lieb, Gregory E Crawford, Terrence S Furey, Ivan Rusyn
Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control of transcription, and understanding of the chemical effects on both could inform the causal role of epigenetic alterations in disease mechanisms. In this study, we hypothesized that baseline variability in chromatin organization and transcription profiles among various tissues and mouse strains influence the outcome of exposure to the DNA damaging chemical 1,3-butadiene...
February 10, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Jie-Fei Miao, Yan-Fu Peng, Shi Chen, Wei-Jie Gao, Qiu-Xing Yang, Peng Zhu, Jing Guo, Jinhua Tao, Lin Luo, Yanan Zhang, Yong Ling
This study aims to design and synthesize a novel harmine derivative N-(4-(hydroxycarbamoyl) benzyl)-1-(4-methoxyphenyl)-9H-pyrido [3,4-b]indole-3-carboxamide (HBC) as histone deacetylase (HDAC) inhibitor, and evaluate its antitumor activities and anti-metastasis mechanism. HBC not only exerted significant ant-proliferation activity against five human cancer cell lines, especially for HepG2 cell with an IC50 value of 2.21μM, which is nearly three-fold lower than SAHA (IC50 = 6.26µM), but also showed selective HDAC1/6 inhibitory effects in vitro...
February 8, 2018: European Journal of Pharmacology
Xiaoming Sun, Lin Lu, Xiudong Liao, Liyang Zhang, Xi Lin, Xugang Luo, Qiugang Ma
The role of in ovo zinc (Zn) injection in improving the embryonic development in eggs from Zn-deficient hens, via epigenetic and antioxidant mechanisms, was examined. A completely randomized design involving a 1 (the non-injected control) + 1 (the injected control with sterilized water) + 2 (Zn source) × 2 (Zn level) factorial arrangement of treatments was used. The two injected Zn sources were inorganic Zn sulfate and organic Zn-lysine chelate with a moderate chelation strength, and the two injected Zn levels were 50 and 100 μg Zn/egg...
February 9, 2018: Biological Trace Element Research
Mi Ra Noh, Chang-Hoon Woo, Mae-Ja Park, Jee In Kim, Kwon Moo Park
Fibrosis is an undesirable consequence of injury and a critical problem in many diseases. Recent studies have demonstrated an association of C/EBP homologous protein (CHOP) with fibrosis. We investigated the mechanism of CHOP in kidney fibrosis progression after unilateral ureteral obstruction (UUO) using Chop gene-deleted (Chop-/-) mice and their wild-type littermates (Chop+/+). UUO-induced kidney fibrosis was reduced in the Chop-/- than Chop+/+ mice. After UUO, CHOP expression was detected in the cytosol and nucleus of distal tubule cells and collecting duct cells of the kidney...
February 6, 2018: Biochimica et Biophysica Acta
Moo Rim Kang, Ki Hwan Park, Chang Woo Lee, Myeong Youl Lee, Sang-Bae Han, Long-Cheng Li, Jong Soon Kang
Recent studies have reported that chemically synthesized double-stranded RNAs (dsRNAs), also known as small activating RNA (saRNAs), can specifically induce gene expression by targeting promoter sequences by a mechanism termed RNA activation (RNAa). In the present study, we designed 4 candidate saRNAs targeting the Von Hippel-Lindau (VHL) gene promoter. Among these saRNAs, dsVHL-821 significantly inhibited cell growth by up-regulating VHL at both the mRNA and protein levels in renal cell carcinoma 769-P cells...
February 6, 2018: International Journal of Biochemistry & Cell Biology
Qing Yu, Anna Jia, Yan Li, Yujing Bi, Guangwei Liu
Microbiota is a group of microbes coexisting and co-evolving with the immune system in the host body for millions of years. There are mutual interaction between microbiota and the immune system. Immune cells can shape the populations of microbiota in the gut of animals and humans, and the presence of microbiota and the microbial products can regulate the development and function of the immune cells in the host. Although microbiota resides mainly at the mucosa, the effect of microbiota on the immune system can be both local at the mucosa and systemic through the whole body...
February 9, 2018: International Reviews of Immunology
Maria A Sacta, Bowranigan Tharmalingam, Maddalena Coppo, David A Rollins, Dinesh K Deochand, Bradley Benjamin, Li Yu, Bin Zhang, Xiaoyu Hu, Rong Li, Yurii Chinenov, Inez Rogatsky
The Glucocorticoid Receptor (GR) potently represses macrophage-elicited inflammation, however, the underlying mechanisms remain obscure. Our genome-wide analysis in mouse macrophages reveals that pro-inflammatory paused genes, activated via global negative elongation factor (NELF) dissociation and RNA Polymerase (Pol)2 release from early elongation arrest, and non-paused genes, induced by de novo Pol2 recruitment, are equally susceptible to acute glucocorticoid repression. Moreover, in both cases the dominant mechanism involves rapid GR tethering to p65 at NF-kB binding sites...
February 9, 2018: ELife
Valerie Migeot, Damien Hermand
The distribution of modified histones within the fission yeast Schizosaccharomyces pombe genome is ultimately dependent upon the transcriptional activity and in turn influences the ability of the polymerases to bind and progress through the chromatin template. The Chromatin Immunoprecipitation-Polymerase Chain Reaction (ChIP-PCR) method currently provides the highest resolution, accuracy, and reproducibility to characterize histones modifications within a defined region of the genome. The following protocol details the method applied to S...
2018: Methods in Molecular Biology
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
Shina Liu, Fei Liu, Weina Huang, Lina Gu, Lingjiao Meng, Yingchao Ju, Yunyan Wu, Juan Li, Lihua Liu, Meixiang Sang
Recently, we have reported that the product of Melanoma Antigens Genes (MAGE) family member MAGE-A11 is an independent poor prognostic marker for esophageal squamous cell carcinoma (ESCC). However, the reason how MAGE-A11 is activated in ESCC progression still remains unclear. In the current study, we demonstrated that DNA methylation and the subsequent histone posttranslational modifications play crucial roles in the regulation of MAGE-A11 in ESCC progression. We found that the methylation rate of TFCP2/ZEB1 binding site on MAGE-A11 promoter in ESCC tissues and cells is higher than the normal esophageal epithelial tissues and cells...
January 9, 2018: Oncotarget
Ji Wu, Hong Zhu, Jianqiang Wu, Wei Chen, Xiaoqing Guan
Development of resistance to doxorubicin-based chemotherapy limits curative effect in breast cancer (BC). N-acetyltransferase 10 (NAT10), a nucleolar protein involved in histone acetylation, is overexpressed in several cancers. We investigated whether NAT10 is involved in doxorubicin resistance in BC and explored the potential mechanisms. Remodelin, a NAT10 inhibitor, and a NAT10 small interfering RNA (siRNA) were used to inhibit NAT10; both remodelin and the NAT10 siRNA reduced cell viability and attenuated doxorubicin resistance in four BC cell lines...
2018: American Journal of Translational Research
Kana Tanabe, Jiaan Liu, Daiki Kato, Hitoshi Kurumizaka, Kenzo Yamatsugu, Motomu Kanai, Shigehiro A Kawashima
Chromatin structure and gene expression are dynamically regulated by posttranslational modifications of histones. Recent advance in mass spectrometry has identified novel types of lysine acylations, such as butyrylation and malonylation, whose functions and regulations are likely different from those of acetylation. Sirtuins, nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases, catalyze various deacylations. However, it is poorly understood how distinct sirtuins regulate the histone acylation states of nucleosomes that have many lysine residues...
February 8, 2018: Scientific Reports
Zsuzsanna Ujfaludi, Agota Tuzesi, Hajnalka Majoros, Balint Rothler, Tibor Pankotai, Imre M Boros
Ultraviolet (UV) B radiation is a dangerous environmental stressor, which can lead to photoaging, inflammation, immune suppression and tumour formation. A recent report has shown the transcriptional activation of several skin-specific genes including matrix metalloproteases (MMPs) in response to UV irradiation. Here, we use a novel human keratinocyte model, HKerE6SFM, to demonstrate that UVB activates the transcription of most members of the 11q22.3 MMP gene cluster including MMP13, MMP12, MMP3, MMP1 and MMP10...
February 8, 2018: Scientific Reports
Ming Zhao, Yixin Tan, Qiao Peng, Cancan Huang, Yu Guo, Gongping Liang, Bochen Zhu, Yi Huang, Aiyun Liu, Zijun Wang, Mengying Li, Xiaofei Gao, Ruifang Wu, Haijing Wu, Hai Long, Qianjin Lu
Epigenetic modifications affect the differentiation of T cell subsets and the pathogenesis of autoimmune diseases, but many mechanisms of epigenetic regulation of T cell differentiation are unclear. Here we show reduced expression of the transcription factor RFX1 in CD4+ T cells from patients with systemic lupus erythematosus, which leads to IL-17A overexpression through increased histone H3 acetylation and decreased DNA methylation and H3K9 tri-methylation. Conditional deletion of Rfx1 in mice exacerbates experimental autoimmune encephalomyelitis and pristane-induced lupus-like syndrome and increases induction of Th17 cells...
February 8, 2018: Nature Communications
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