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histone acetyltransferase

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https://www.readbyqxmd.com/read/29050320/epigenetic-regulation-of-interleukin-8-expression-by-class-i-hdac-and-cbp-in-ovarian-cancer-cells
#1
Himavanth R Gatla, Yue Zou, Mohammad M Uddin, Ivana Vancurova
Although inhibitors of epigenetic regulators have been effective in the treatment of cutaneous T cell lymphoma (CTCL) and other hematopoietic malignancies, they have been less effective in solid tumors, including ovarian cancer (OC). We have previously shown that inhibition of histone deacetylase (HDAC) activity induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (CXCL8, IL-8) in OC cells, resulting in their increased survival and proliferation. Here, we show that in addition to ovarian cancer SKOV3, OVCAR3, and CAOV3 cells, HDAC inhibition induces the CXCL8 expression in HeLa cells, but not in CTCL Hut-78 cells...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049411/xrcc5-cooperates-with-p300-to-promote-cyclooxygenase-2-expression-and-tumor-growth-in-colon-cancers
#2
Zhifeng Zhang, Fufu Zheng, Zhenlong Yu, Jiajiao Hao, Miao Chen, Wendan Yu, Wei Guo, Yiming Chen, Wenlin Huang, Zhijun Duan, Wuguo Deng
Cyclooxygenase (COX) is the rate-limiting enzyme in prostaglandins (PGs) biosynthesis. Previous studies indicate that COX-2, one of the isoforms of COX, is highly expressed in colon cancers and plays a key role in colon cancer carcinogenesis. Thus, searching for novel transcription factors regulating COX-2 expression will facilitate drug development for colon cancer. In this study, we identified XRCC5 as a binding protein of the COX-2 gene promoter in colon cancer cells with streptavidin-agarose pulldown assay and mass spectrometry analysis, and found that XRCC5 promoted colon cancer growth through modulation of COX-2 signaling...
2017: PloS One
https://www.readbyqxmd.com/read/29046054/porphyromonas-gingivalis-lipopolysaccharide-stimulation-in-human-periodontal-ligament-stem-cells-role-of-epigenetic-modifications-to-the-inflammation
#3
Francesca Diomede, Soundara Rajan Thangavelu, Ilaria Merciaro, Monica D'Orazio, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Periodontitis is a chronic oral inflammatory disease produced by bacteria. Gingival retraction and bone and connective tissues resorption are the hallmarks of this disease. Chronic periodontitis may contribute to the risk of onset or progression of neuroinflammatory pathological conditions, such as Alzheimer's disease. The main goal of the present study was to investigate if the role of epigenetic modulations is involved in periodontitis using human periodontal ligament stem cells (hPDLSCs) as an in vitro model system...
August 25, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/29035278/hdac3-regulates-lymphovenous-and-lymphatic-valve-formation
#4
Harish P Janardhan, Zachary J Milstone, Masahiro Shin, Nathan D Lawson, John F Keaney, Chinmay M Trivedi
Lymphedema, the most common lymphatic anomaly, involves defective lymphatic valve development; yet the epigenetic modifiers underlying lymphatic valve morphogenesis remain elusive. Here, we showed that during mouse development, the histone-modifying enzyme histone deacetylase 3 (Hdac3) regulates the formation of both lymphovenous valves, which maintain the separation of the blood and lymphatic vascular systems, and the lymphatic valves. Endothelium-specific ablation of Hdac3 in mice led to blood-filled lymphatic vessels, edema, defective lymphovenous valve morphogenesis, improper lymphatic drainage, defective lymphatic valve maturation, and complete lethality...
October 16, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29033323/mtorc1-phosphorylates-acetyltransferase-p300-to-regulate-autophagy-and-lipogenesis
#5
Wei Wan, Zhiyuan You, Yinfeng Xu, Li Zhou, Zhunlv Guan, Chao Peng, Catherine C L Wong, Hua Su, Tianhua Zhou, Hongguang Xia, Wei Liu
Acetylation is increasingly recognized as one of the major post-translational mechanisms for the regulation of multiple cellular functions in mammalian cells. Acetyltransferase p300, which acetylates histone and non-histone proteins, has been intensively studied in its role in cell growth and metabolism. However, the mechanism underlying the activation of p300 in cells remains largely unknown. Here, we identify the homeostatic sensor mTORC1 as a direct activator of p300. Activated mTORC1 interacts with p300 and phosphorylates p300 at 4 serine residues in the C-terminal domain...
October 11, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29030587/natd-promotes-lung-cancer-progression-by-preventing-histone-h4-serine-phosphorylation-to-activate-slug-expression
#6
Junyi Ju, Aiping Chen, Yexuan Deng, Ming Liu, Ying Wang, Yadong Wang, Min Nie, Chao Wang, Hong Ding, Bing Yao, Tao Gui, Xinyu Li, Zhen Xu, Chi Ma, Yong Song, Marc Kvansakul, Ke Zen, Chen-Yu Zhang, Cheng Luo, Ming Fang, David C S Huang, C David Allis, Renxiang Tan, Changjiang Kathy Zeng, Jiwu Wei, Quan Zhao
N-α-acetyltransferase D (NatD) mediates N-α-terminal acetylation (Nt-acetylation) of histone H4 known to be involved in cell growth. Here we report that NatD promotes the migratory and invasive capabilities of lung cancer cells in vitro and in vivo. Depletion of NatD suppresses the epithelial-to-mesenchymal transition (EMT) of lung cancer cells by directly repressing the expression of transcription factor Slug, a key regulator of EMT. We found that Nt-acetylation of histone H4 antagonizes histone H4 serine 1 phosphorylation (H4S1ph), and that downregulation of Nt-acetylation of histone H4 facilitates CK2α binding to histone H4 in lung cancer cells, resulting in increased H4S1ph and epigenetic reprogramming to suppress Slug transcription to inhibit EMT...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29028833/merkel-cell-polyomavirus-recruits-mycl-to-the-ep400-complex-to-promote-oncogenesis
#7
Jingwei Cheng, Donglim Esther Park, Christian Berrios, Elizabeth A White, Reety Arora, Rosa Yoon, Timothy Branigan, Tengfei Xiao, Thomas Westerling, Alexander Federation, Rhamy Zeid, Benjamin Strober, Selene K Swanson, Laurence Florens, James E Bradner, Myles Brown, Peter M Howley, Megha Padi, Michael P Washburn, James A DeCaprio
Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29023392/disposition-metabolism-and-histone-deacetylase-and-acetyltransferase-inhibition-activity-of-tetrahydrocurcumin-and-other-curcuminoids
#8
Júlia T Novaes, Ryan Lillico, Casey L Sayre, Kalyanam Nagabushnam, Muhammed Majeed, Yufei Chen, Emmanuel A Ho, Ana Luísa de P Oliveira, Stephanie E Martinez, Samaa Alrushaid, Neal M Davies, Ted M Lakowski
Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC-MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate...
October 12, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/29021135/histone-acetyltransferase-kat6a-upregulates-pi3k-akt-signaling-through-trim24-binding
#9
Deguan Lv, Feng Jia, Yanli Hou, Youzhou Sang, Angel A Alvarez, Weiwei Zhang, Wei-Qiang Gao, Bo Hu, Shi-Yuan Cheng, Jianwei Ge, Yanxin Li, Haizhong Feng
Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM) where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/29018219/spatially-restricted-loading-of-brd2-at-dna-double-strand-breaks-protects-h4-acetylation-domains-and-promotes-dna-repair
#10
Ozge Gursoy-Yuzugullu, Chelsea Carman, Brendan D Price
The n-terminal tail of histone H4 recruits repair proteins, including 53BP1, to DNA double-strand breaks (DSB) and undergoes dynamic acetylation during DSB repair. However, how H4 acetylation (H4Ac) recruits repair proteins and reorganizes chromatin during DNA repair is unclear. Here, we show that the bromodomain protein BRD2 is recruited to DSBs. This recruitment requires binding of BRD2's tandem bromodomains to H4Ac, which is generated at DSBs by the Tip60/KAT5 acetyltransferase. Binding of BRD2 to H4Ac protects the underlying acetylated chromatin from attack by histone deacetylases and allows acetylation to spread along the flanking chromatin...
October 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29018172/foxo1-and-foxp1-play-opposing-roles-in-regulating-the-differentiation-and-antitumor-activity-of-th9-cells-programmed-by-il-7
#11
Enguang Bi, Xingzhe Ma, Yong Lu, Maojie Yang, Qiang Wang, Gang Xue, Jianfei Qian, Siqing Wang, Qing Yi
Tumor-specific CD4(+) T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naïve CD4(+) T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter...
October 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28991411/structural-insights-into-the-nuclear-import-of-the-histone-acetyltransferase-mof-by-importin-%C3%AE-1
#12
Weili Zheng, Rui Wang, Xi Liu, Siyu Tian, Benqiang Yao, Ang Chen, Shikai Jin, Yong Li
The histone acetyltransferase MOF (males-absent-on-the-first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive...
October 9, 2017: Traffic
https://www.readbyqxmd.com/read/28981106/nlrp3-inflammasome-activation-contributes-to-vsmc-phenotypic-transformation-and-proliferation-in-hypertension
#13
Hai-Jian Sun, Xing-Sheng Ren, Xiao-Qing Xiong, Yun-Zhi Chen, Ming-Xia Zhao, Jue-Jin Wang, Ye-Bo Zhou, Ying Han, Qi Chen, Yue-Hua Li, Yu-Ming Kang, Guo-Qing Zhu
Inflammation is involved in pathogenesis of hypertension. NLRP3 inflammasome activation is a powerful mediator of inflammatory response via caspase-1 activation. The present study was designed to determine the roles and mechanisms of NLRP3 inflammasome in phenotypic modulation and proliferation of vascular smooth muscle cells (VSMCs) in hypertension. Experiments were conducted in spontaneously hypertensive rats (SHR) and primary aortic VSMCs. NLRP3 inflammasome activation was observed in the media of aorta in SHR and in the VSMCs from SHR...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979238/n-acetylaspartate-metabolism-outside-the-brain-lipogenesis-histone-acetylation-and-cancer
#14
REVIEW
Juliane G Bogner-Strauss
N-acetylaspartate (NAA) is a highly abundant brain metabolite. Aberrant NAA concentrations have been detected in many pathological conditions and although the function of NAA has been extensively investigated in the brain it is still controversial. Only recently, a role of NAA has been reported outside the brain. In brown adipocytes, which show high expression of the NAA-producing and the NAA-cleaving enzyme, the metabolism of NAA has been implicated in lipid synthesis and histone acetylation. Increased expression of N-acetyltransferase 8-like (Nat8l, the gene encoding the NAA synthesizing enzyme) induces de novo lipogenesis and the brown adipocyte phenotype...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28977641/pp32-and-set-taf-i%C3%AE-proteins-regulate-the-acetylation-of-newly-synthesized-histone-h4
#15
Francisco Saavedra, Carlos Rivera, Elizabeth Rivas, Paola Merino, Daniel Garrido, Sergio Hernández, Ignasi Forné, Isabelle Vassias, Zachary A Gurard-Levin, Iván E Alfaro, Axel Imhof, Geneviève Almouzni, Alejandra Loyola
Newly synthesized histones H3 and H4 undergo a cascade of maturation steps to achieve proper folding and to establish post-translational modifications prior to chromatin deposition. Acetylation of H4 on lysines 5 and 12 by the HAT1 acetyltransferase is observed late in the histone maturation cascade. A key question is to understand how to establish and regulate the distinct timing of sequential modifications and their biological significance. Here, we perform proteomic analysis of the newly synthesized histone H4 complex at the earliest time point in the cascade...
August 30, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28976802/the-mixed-lineage-leukemia-4-mll4-methyltransferase-complex-is-involved-in-transforming-growth-factor-beta-tgf-%C3%AE-activated-gene-transcription
#16
Roy Baas, Hetty A A M van Teeffelen, Sjoerd J D Tjalsma, H Th Marc Timmers
Sma and Mad related (SMAD)-mediated Transforming Growth Factor β (TGF-β) and Bone Morphogenetic Protein (BMP) signaling is required for various cellular processes. The activated heterotrimeric SMAD protein complexes associate with nuclear proteins such as the histone acetyltransferases p300, PCAF and the Mixed Lineage Leukemia 4 (MLL4) subunit Pax Transactivation domain-Interacting Protein (PTIP) to regulate gene transcription. We investigated the functional role of PTIP and PTIP Interacting protein 1 (PA1) in relation to TGF-β-activated SMAD signaling...
October 4, 2017: Transcription
https://www.readbyqxmd.com/read/28973931/systems-level-identification-of-pka-dependent-signaling-in-epithelial-cells
#17
Kiyoshi Isobe, Hyun Jun Jung, Chin-Rang Yang, J'Neka Claxton, Pablo Sandoval, Maurice B Burg, Viswanathan Raghuram, Mark A Knepper
G protein stimulatory α-subunit (Gαs)-coupled heptahelical receptors regulate cell processes largely through activation of protein kinase A (PKA). To identify signaling processes downstream of PKA, we deleted both PKA catalytic subunits using CRISPR-Cas9, followed by a "multiomic" analysis in mouse kidney epithelial cells expressing the Gαs-coupled V2 vasopressin receptor. RNA-seq (sequencing)-based transcriptomics and SILAC (stable isotope labeling of amino acids in cell culture)-based quantitative proteomics revealed a complete loss of expression of the water-channel gene Aqp2 in PKA knockout cells...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28972079/histone-deacetylase-is-required-for-ga-induced-programmed-cell-death-in-maize-aleurone-layers
#18
Haoli Hou, Xueke Zheng, Hao Zhang, Mengxia Yue, Yan Hu, Hong Zhou, Qing Wang, Chensheng Xie, Pu Wang, Lijia Li
Recent discoveries have shown that epigenetic regulation is an integral part of phytohormone-mediated processes. The phytohormone gibberellic acid (GA) triggers a series of events in cereal aleurone cells that lead to programmed cell death (PCD), but the signaling cascade mediating GA-induced PCD in cereal aleurone layers remains largely unknown. Here, we showed that histone deacetylase (HDAC) activity gradually increased relative to histone acetyltransferase (HAT) activity, leading to a global decrease in histone H3 and H4 acetylation levels during PCD of maize embryoless aleurone layers after 3 d of treatment with GA...
September 29, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28971961/integument-development-in%C3%A2-arabidopsis-depends-on-interaction-of-yabby-protein-inner-no-outer-with-co-activators-and-co-repressors
#19
Marissa K Simon, Debra J Skinner, Thomas L Gallagher, Charles S Gasser
Arabidopsis thaliana INNER NO OUTER (INO) is a YABBY protein that is essential for initiation and development of the outer integument of ovules. Other YABBY proteins have been shown to be involved in both negative and positive regulation of expression of putative target genes. YABBY proteins have also been shown to interact with the co-repressor LEUNIG (LUG) in several systems. In support of a repressive role for INO we confirm that INO interacts with LUG, and also find that INO directly interacts with SEUSS (SEU), a known co-repressive partner of LUG...
September 29, 2017: Genetics
https://www.readbyqxmd.com/read/28971711/epigenetic-regulation-in-bacterial-infections-targeting-histone-deacetylases
#20
Aleksander M Grabiec, Jan Potempa
Pathogens have developed sophisticated strategies to evade the immune response, among which manipulation of host cellular epigenetic mechanisms plays a prominent role. In the last decade, modulation of histone acetylation in host cells has emerged as an efficient strategy of bacterial immune evasion. Virulence factors and metabolic products of pathogenic microorganisms alter expression and activity of histone acetyltransferases (HATs) and histone deacetylases (HDACs) to suppress transcription of host defense genes through epigenetic changes in histone acetylation marks...
October 3, 2017: Critical Reviews in Microbiology
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