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histone acetyltransferase

Maria E Ramirez-Roman, Carlos E Billini, Alfredo Ghezzi
Alcohol addiction is a serious condition perpetuated by enduring physiological and behavioral adaptations. An important component of these adaptations is the long-term rearrangement of neuronal gene expression in the brain of the addicted individual. Epigenetic histone modifications have recently surfaced as important modulators of the transcriptional adaptation to alcohol as these are thought to represent a form of transcriptional memory that is directly imprinted on the chromosome. Some histone modifications affect transcription by modulating the accessibility of the underlying DNA, whereas others have been proposed to serve as marks read by transcription factors as a "histone code" that helps to specify the expression level of a gene...
2018: Journal of Experimental Neuroscience
Sarah Kerns, Kuang-Hsiang Chuang, William Hall, Zachary Werner, Yuhchyau Chen, Harry Ostrer, Catharine West, Barry Rosenstein
Radiobiology research is building the foundation for applying genomics in precision radiation oncology. Advances in high-throughput approaches will underpin increased understanding of radiosensitivity and the development of future predictive assays for clinical application. There is an established contribution of genetics as a risk factor for radiotherapy side-effects. An individual's radiosensitivity is an inherited polygenic trait with an architecture that includes rare mutations in a few genes that confer large effects and common variants in many genes with small effects...
June 11, 2018: British Journal of Radiology
Veronica Garcia-Carpizo, Sergio Ruiz-Llorente, Jacinto Sarmentero, Osvaldo Graña-Castro, David G Pisano, Maria J Barrero
BACKGROUND: The reported antitumor activity of the BET family bromodomain inhibitors has prompted the development of inhibitors against other bromodomains. However, the human genome encodes more than 60 different bromodomains and most of them remain unexplored. RESULTS: We report that the bromodomains of the histone acetyltransferases CREBBP/EP300 are critical to sustain the proliferation of human leukemia and lymphoma cell lines. EP300 is very abundant at super-enhancers in K562 and is coincident with sites of GATA1 and MYC occupancy...
June 8, 2018: Epigenetics & Chromatin
Amit Kumar Singh, Anupam Bishayee, Abhay K Pandey
Cancer initiation and progression are the result of genetic and/or epigenetic alterations. Acetylation-mediated histone/non-histone protein modification plays an important role in the epigenetic regulation of gene expression. Histone modification is controlled by the balance between histone acetyltransferase and (HAT) and histone deacetylase (HDAC) enzymes. Imbalance between the activities of these two enzymes is associated with various forms of cancer. Histone deacetylase inhibitors (HDACi) regulate the activity of HDACs and are being used in cancer treatment either alone or in combination with other chemotherapeutic drugs/radiotherapy...
June 6, 2018: Nutrients
Xue Hou, Run Gong, Jianhua Zhan, Ting Zhou, Yuxiang Ma, Yuanyuan Zhao, Yaxiong Zhang, Gang Chen, Zhonghan Zhang, Shuxiang Ma, Xi Chen, Fangfang Gao, Shaodong Hong, Fan Luo, Wenfeng Fang, Yunpeng Yang, Yan Huang, Likun Chen, Haoxian Yang, Li Zhang
BACKGROUND: Histone acetyltransferase p300 is a crucial transcriptional coactivator and has been implicated as a poor prognostic factor in human cancers. However, little is known about the substantial functions and mechanisms of p300 in NSCLC proliferation and distant metastasis. METHODS: We constructed p300 down-regulated and up-regulated cell lines through RNAi and recombinant plasmid transfection. Cell Counting Kit-8 assays were used to test the cell proliferation and confirmed by colony formation assays...
June 7, 2018: BMC Cancer
Anastasia Z Kalea, Konstantinos Drosatos, Jessica L Buxton
PURPOSE OF REVIEW: We present a current perspective of epigenetic alterations that can lead to cardiovascular disease (CVD) and the potential of dietary factors to counteract their actions. In addition, we discuss the challenges and opportunities of dietary treatments as epigenetic modifiers for disease prevention and therapy. RECENT FINDINGS: Recent epigenome-wide association studies along with candidate gene approaches and functional studies in cell culture and animal models have delineated mechanisms through which nutrients, food compounds and dietary patterns may affect the epigenome...
July 2018: Current Opinion in Clinical Nutrition and Metabolic Care
Jenna Kotak, Marina Saisana, Vasilis Gegas, Nikoletta Pechlivani, Athanasios Kaldis, Panagiotis Papoutsoglou, Athanasios Makris, Julia Burns, Ashley L Kendig, Minnah Sheikh, Cyrus E Kuschner, Gabrielle Whitney, Hanna Caiola, John H Doonan, Konstantinos E Vlachonasios, Elizabeth R McCain, Amy T Hark
The histone acetyltransferase GCN5 and associated transcriptional coactivator ADA2b are required to couple endoreduplication and trichome branching. Mutation of ADA2b also disrupts the relationship between ploidy and leaf cell size. Dynamic chromatin structure has been established as a general mechanism by which gene function is temporally and spatially regulated, but specific chromatin modifier function is less well understood. To address this question, we have investigated the role of the histone acetyltransferase GCN5 and the associated coactivator ADA2b in developmental events in Arabidopsis thaliana...
May 30, 2018: Planta
Qian Zhang, Oren Akhberdi, Dongsheng Wei, Longfei Chen, Heng Liu, Dan Wang, Xiaoran Hao, Xudong Zhu
Reverse genetics is a promising strategy for elucidating the regulatory mechanisms involved in secondary metabolism and development in fungi. Previous studies have demonstrated the key role of histone acetyltransferases in transcriptional regulation. Here, we identified a MYST family histone acetyltransferase encoding gene, mst2, in the filamentous fungus Pestalotiopsis microspora NK17 and revealed its role in development and secondary metabolism. The gene mst2 showed temporal expression that corresponded to the conidiation process in the wild-type strain...
May 29, 2018: Scientific Reports
Mari Ichihara, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
Superoxide dismutase 3 (SOD3) is a SOD isozyme and plays a key role in extracellular redox homeostasis. We previously demonstrated that histone acetylation is involved in 12-O-tetra-decanoylphorbol-13-acetate (TPA)-elicited SOD3 expression in human monocytic THP-1 cells; however, the molecular mechanisms responsible for its expression have not yet been elucidated in detail. The results of the present study demonstrated that the binding of histone deacetylase 1 (HDAC1) to the SOD3 promoter region contributed to SOD3 silencing in basal THP-1 cells...
May 29, 2018: Free Radical Research
Brian T Weinert, Takeo Narita, Shankha Satpathy, Balaji Srinivasan, Bogi K Hansen, Christian Schölz, William B Hamilton, Beth E Zucconi, Wesley W Wang, Wenshe R Liu, Joshua M Brickman, Edward A Kesicki, Albert Lai, Kenneth D Bromberg, Philip A Cole, Chunaram Choudhary
The acetyltransferases CBP and p300 are multifunctional transcriptional co-activators. Here, we combined quantitative proteomics with CBP/p300-specific catalytic inhibitors, bromodomain inhibitor, and gene knockout to reveal a comprehensive map of regulated acetylation sites and their dynamic turnover rates. CBP/p300 acetylates thousands of sites, including signature histone sites and a multitude of sites on signaling effectors and enhancer-associated transcriptional regulators. Time-resolved acetylome analyses identified a subset of CBP/p300-regulated sites with very rapid (<30 min) acetylation turnover, revealing a dynamic balance between acetylation and deacetylation...
May 14, 2018: Cell
Andrew N Rouble, Liam J Hawkins, Kenneth B Storey
The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) is a well-known model for studying hibernation. While in a torpid state, these animals globally suppress energy expensive processes, while supporting specialized pathways necessary for survival. Lysine acetyltransferases (KATs) play a crucial role in modulating the expression and activity of a wide-variety of cellular pathways and processes, and therefore, may play a role during hibernation when the cell is shifting to an energy conservative, cytoprotective state...
May 2018: Journal of Thermal Biology
Hanwei Jiang, Qian Gao, Wei Zheng, Shi Yin, Liu Wang, Liangwen Zhong, Asim Ali, Teka Khan, Qiaomei Hao, Hui Fang, Xiaoling Sun, Peng Xu, Tej K Pandita, Xiaohua Jiang, Qinghua Shi
Three waves of H2AX phosphorylation (γH2AX) have been observed in male meiotic prophase I: the first is ATM-dependent and occurs at leptonema, while the second and third are ATR-dependent, occuring at zygonema and pachynema, respectively. The third wave of H2AX phosphorylation marks and silences unsynapsed chromosomes. Little is known about H2AX phosphorylation expands to chromatin-wide regions in spermatocytes. Here, we report that histone acetyltransferase (HAT) MOF is involved in all three waves of H2AX phosphorylation expansion...
May 24, 2018: PLoS Genetics
Kyounghee Lee, Pil Joon Seo
The histone acetyltransferase HAF2 facilitates H3 acetylation deposition at the PRR5 and LUX promoters to contribute to robust circadian oscillation. The circadian clock ensures synchronization of endogenous rhythmic processes with environmental cycles. Multi-layered regulation underlies precise circadian oscillation, and epigenetic regulation is emerging as a crucial scheme for robust circadian maintenance. Here, we report that HISTONE ACETYLTRANSFERASE OF THE TAFII250 FAMILY 2 (HAF2) is involved in circadian homeostasis...
May 22, 2018: Planta
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
Maria Gabriella Matera, Luigino Calzetta, Giulia Gritti, Laura Gallo, Brunella Perfetto, Giovanna Donnarumma, Mario Cazzola, Paola Rogliani, Maria Donniacuo, Barbara Rinaldi
In patients with chronic obstructive pulmonary disease (COPD) the inflammatory response is often steroid-resistant, likely since oxidative stress and cigarette smoking impair histone deacetylase 2 (HDAC2) activity. Since it has been demonstrated that statins may restore the HDAC2 activity in cultured human endothelial cells, the aim of this study was to investigate the effects of statins in reversing the steroid-resistance induced by oxidative stress. We evaluated the effects of simvastatin and dexamethasone on HDAC2 expression and activity, and the role of mevalonate and Rho/ROCK pathways in A549 cells, a human lung type II epithelial cell line stressed with H2 O2 ...
May 18, 2018: European Journal of Pharmacology
Gao-Shang Chai, Qiong Feng, Rong-Hong Ma, Xiao-Hang Qian, Dan-Ju Luo, Zhi-Hao Wang, Yu Hu, Dong-Sheng Sun, Jun-Fei Zhang, Xiao Li, Xiao-Guang Li, Dan Ke, Jian-Zhi Wang, Xi-Fei Yang, Gong-Ping Liu
There is accumulating evidence that decreased histone acetylation is involved in normal aging and neurodegenerative diseases. Recently, we found that ANP32A, a key component of INHAT (inhibitor of acetyltransferases) that suppresses histone acetylation, increased in aged and cognitively impaired C57 mice and expressing wild-type human full length tau (htau) transgenic mice. Downregulating ANP32A restored cognitive function and synaptic plasticity through upregulation of the expressions of synaptic-related proteins via increasing histone acetylation...
May 16, 2018: Journal of Alzheimer's Disease: JAD
Xiangjiu Kong, Anne D van Diepeningen, Theo A J van der Lee, Cees Waalwijk, Jingsheng Xu, Jin Xu, Hao Zhang, Wanquan Chen, Jie Feng
Post-translational modifications of chromatin structure by histone acetyltransferase (HATs) play a central role in the regulation of gene expression and various biological processes in eukaryotes. Although HAT genes have been studied in many fungi, few of them have been functionally characterized. In this study, we identified and characterized four putative HATs ( FgGCN5, FgRTT109, FgSAS2, FgSAS3 ) in the plant pathogenic ascomycete Fusarium graminearum , the causal agent of Fusarium head blight of wheat and barley...
2018: Frontiers in Microbiology
Xudong Guo, Yanxin Xu, Zikang Wang, Yukang Wu, Jiayu Chen, Guiying Wang, Chenqi Lu, Wenwen Jia, Jiajie Xi, Songcheng Zhu, Zeyidan Jiapaer, Xiaoping Wan, Zhongmin Liu, Shaorong Gao, Jiuhong Kang
Large intergenic non-coding RNAs (lincRNAs) play widespread roles in epigenetic regulation during multiple differentiation processes, but little is known about their mode of action in cardiac differentiation. Here, we identified the key roles of a lincRNA, termed linc1405, in modulating the core network of cardiac differentiation by functionally interacting with Eomes. Chromatin- and RNA-immunoprecipitation assays showed that exon 2 of linc1405 physically mediates a complex consisting of Eomes, trithorax group (TrxG) subunit WDR5, and histone acetyltransferase GCN5 binding at the enhancer region of Mesp1 gene and activates its expression during cardiac mesoderm specification of embryonic stem cells...
May 3, 2018: Cell Stem Cell
Hong Kim, So-Young Lee, Yu-Min Choi, Bum-Joon Kim
Here, we found that a 6-mer peptide, Poly6, derived from the hepatitis B virus (HBV), which overlaps with a polymerase corresponding to a preS1 deletion reported to contribute to liver disease progression, can elicit an antiviral effect against human immunodeficiency virus (HIV)-1 by inhibiting HIV-1 integrase (IN) activity of infected cells. Mechanistic studies revealed that the anti-HIV-1 effects of Poly6 occurred via the inhibition of integration, which resulted from the inhibition of acetylation of HIV-1 IN possibly by downregulation of p300 histone acetyltransferase...
May 9, 2018: Biochemical and Biophysical Research Communications
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