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histone acetyltransferase

Francesco Fiorentino, Antonello Mai, Dante Rotili
Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents...
April 20, 2018: Future Medicinal Chemistry
Wilson R Sinclair, Jonathan H Shrimp, Thomas T Zengeya, Rhushikesh A Kulkarni, Julie M Garlick, Hans Luecke, Andrew J Worth, Ian A Blair, Nathaniel W Snyder, Jordan L Meier
Short chain fatty acids (SCFAs) play a central role in health and disease. One function of these signaling molecules is to serve as precursors for short chain fatty acylation, a class of metabolically-derived posttranslational modifications (PTMs) that are established by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Via this mechanism, short chain fatty acylation serves as an integrated reporter of metabolism as well as KAT and KDAC activity, and has the potential to illuminate the role of these processes in disease...
February 7, 2018: Chemical Science
Emma Bondy-Chorney, Alix Denoncourt, Yuka Sai, Michael Downey
Lysine acetylation is a critical post-translation modification that can impact a protein's localization, stability and function. Originally thought to only occur on histones, we now know thousands of non-histone proteins are also acetylated. In conjunction with many other proteins, lysine acetyltransferases (KATs) are incorporated into large protein complexes that carry out these modifications. In this review we focus on the contribution of two KATs, KAT2A and KAT2B, and their potential roles in the development and progression of cancer...
April 19, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Matt C Danzi, Nick O'Neill, John L Bixby, Vance P Lemmon
Several studies have demonstrated that the intrinsic ability of neurons to regenerate their axons can be stimulated by maneuvers that favor the open state of chromatin, such as inhibiting histone deacetylase activity or increasing histone acetyltransferase activity. Taken together, these experiments suggest that axon regenerative ability can be increased by promoting chromatin accessibility. In this review, we assess the direct evidence in the literature for this hypothesis and re-examine other axon regeneration-promoting manipulations to see if they provide additional support...
April 17, 2018: Developmental Neurobiology
Yunting Jian, Meng Wang, Yan Zhang, Ruizhang Ou, Ziyuan Zhu, Yangying Ou, Xiangfu Chen, Xin Liang, Yanqing Ding, Libing Song, Xuehu Xu, Wenting Liao
Jade family PHD finger 3 (JADE3) plays a role in inducing histone acetylation during transcription, and is involved in the progression of several human cancers; however, its role in colon cancer remains unclear. Herein, we found that JADE3 was markedly upregulated in colon cancer tissues and significantly correlated with cancer progression, and predicted shorter patient survival. Further, JADE3 was expressed much higher in colon cancer cell lines that are enriched with a stem-like signature. Overexpression of JADE3 increased, while silencing JADE3 reduced cancer stem cell-like traits in colon cancer cells in vitro and in vivo...
April 13, 2018: Cancer Letters
Bei-Ping Miao, Rui-Shi Zhang, Gui Yang, Jin-Jie Sun, Yu-Yan Tang, Wei-Feng Liang, Tao Liu, Zhong Wen, Ping-Chang Yang, Guo-Hui Nie
The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry...
April 2, 2018: Archives of Biochemistry and Biophysics
A Milosavljević, Lj DJukić, B Toljić, J Milašin, B DŽeletović, B Brković, J Roganović
AIM: To investigate melatonin (MEL) levels in human dental pulp tissue (hDP) in type 2 diabetic (T2D) participants and underlying molecular mechanisms of its effects in human dental pulp cells (hDPCs) under hyperglycemia. METHODOLOGY: The study included 16 healthy and 16 T2D participants who underwent vital pulp extirpation for hDP and 4 healthy participants undergoing third molar extraction for hDPCs analyses. MTT and NRU were used as tests for cytotoxicity. The pulp tissue levels of MEL, inducible NO synthase (iNOS) and superoxide dismutase (SOD) activity, as well as iNOS, histone acetyltransferase p300 (p300) and SOD activity levels in hDPCs incubated with MEL (0...
April 4, 2018: International Endodontic Journal
Milena S Espíndola, Luana S Soares, Leonardo J Galvão-Lima, Fabiana A Zambuzi, Maira C Cacemiro, Verônica S Brauer, Cleni M Marzocchi-Machado, Matheus de Souza Gomes, Laurence R Amaral, Olindo A Martins-Filho, Valdes R Bollela, Fabiani G Frantz
Monocytes are key cells in the immune dysregulation observed during human immunodeficiency virus (HIV) infection. The events that take place specifically in monocytes may contribute to the systemic immune dysfunction characterized by excessive immune activation in infected individuals, which directly correlates with pathogenesis and progression of the disease. Here, we investigated the immune dysfunction in monocytes from untreated and treated HIV + patients and associated these findings with epigenetic changes...
April 3, 2018: Scientific Reports
Yoichi Sunagawa, Masafumi Funamoto, Shogo Sono, Kana Shimizu, Satoshi Shimizu, Mai Genpei, Yusuke Miyazaki, Yasufumi Katanasaka, Eriko Morimoto, Morio Ueno, Maki Komiyama, Hideaki Kakeya, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
The natural compound, curcumin (CUR), possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT) inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy...
March 13, 2018: Journal of Pharmacological Sciences
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Maki Wakamiya, Roberto P Garofalo, Allan R Brasier
Lower respiratory tract infection with respiratory syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role of adaptive immunity in RSV infection, the identity of the major sentinel cells initially triggering inflammation is controversial. Here we evaluate the role of nonciliated secretoglobin ( Scgb1a1 )-expressing bronchiolar epithelial cells in RSV infection. Knock-in mice expressing a tamoxifen (TMX)-inducible Cre recombinase (CreERTM ) from the Scgb1a1 locus were crossed with mice that harbor a RelA conditional allele ( RelAfl ), with loxP sites flanking exons 5-8 of the Rel homology domain...
March 28, 2018: Journal of Virology
Takeshi Yasuda, Wataru Kagawa, Tomoo Ogi, Takamitsu A Kato, Takehiro Suzuki, Naoshi Dohmae, Kazuya Takizawa, Yuka Nakazawa, Matthew D Genet, Mika Saotome, Michio Hama, Teruaki Konishi, Nakako Izumi Nakajima, Masaharu Hazawa, Masanori Tomita, Manabu Koike, Katsuko Noshiro, Kenichi Tomiyama, Chizuka Obara, Takaya Gotoh, Ayako Ui, Akira Fujimori, Fumiaki Nakayama, Fumio Hanaoka, Kaoru Sugasawa, Ryuichi Okayasu, Penny A Jeggo, Katsushi Tajima
The p300 and CBP histone acetyltransferases are recruited to DNA double-strand break (DSB) sites where they induce histone acetylation, thereby influencing the chromatin structure and DNA repair process. Whether p300/CBP at DSB sites also acetylate non-histone proteins, and how their acetylation affects DSB repair, remain unknown. Here we show that p300/CBP acetylate RAD52, a human homologous recombination (HR) DNA repair protein, at DSB sites. Using in vitro acetylated RAD52, we identified 13 potential acetylation sites in RAD52 by a mass spectrometry analysis...
March 28, 2018: PLoS Genetics
Martine Chevillard-Briet, Fabrice Escaffit
Since chromatin-modifying enzymes are involved in most processes needing to access the DNA fiber such as transcription, replication or DNA repair, their involvement in the regulation of gene expression in numerous physiopathological contexts is widely studied. Most of these enzymes are essential for cell growth and survival due to their pleiotropic roles and studying their impact in vivo on organ development or tissue physiopathology is challenging. In this chapter, we describe a chemically-mediated method to induce colorectal carcinogenesis that we have used to identify in vivo the role of two chromatin modifying enzymes belonging to the same multimolecular complex, the histone acetyltransferase Tip60 and the histone variant-incorporating ATPase p400...
2018: Methods in Molecular Biology
Zhao Wang, Lindsey W Plasschaert, Shivani Aryal, Nicole A Renaud, Zinger Yang, Rayman Choo-Wing, Angelica D Pessotti, Nathaniel D Kirkpatrick, Nadire R Cochran, Walter Carbone, Rob Maher, Alicia Lindeman, Carsten Russ, John Reece-Hoyes, Gregory McAllister, Gregory R Hoffman, Guglielmo Roma, Aron B Jaffe
The multiciliated cell (MCC) is an evolutionarily conserved cell type, which in vertebrates functions to promote directional fluid flow across epithelial tissues. In the conducting airway, MCCs are generated by basal stem/progenitor cells and act in concert with secretory cells to perform mucociliary clearance to expel pathogens from the lung. Studies in multiple systems, including Xenopus laevis epidermis, murine trachea, and zebrafish kidney, have uncovered a transcriptional network that regulates multiple steps of multiciliogenesis, ultimately leading to an MCC with hundreds of motile cilia extended from their apical surface, which beat in a coordinated fashion...
March 27, 2018: Journal of Cell Biology
Rosa Ferriero, Edoardo Nusco, Rossella De Cegli, Annamaria Carissimo, Giuseppe Manco, Nicola Brunetti-Pierri
BACKGROUND AND AIMS: Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. METHODS: Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen...
March 23, 2018: Journal of Hepatology
Qing Cai, Zhi-Kang Wang, Wei Shao, Sheng-Hua Ying, Ming-Guang Feng
Rpd3 is a class I histone deacetylase that reverses lysine acetylation thus influencing cellular processes and functions. However, its role in fungal insect pathogens has not been explored yet. Here we show that Rpd3-dependent lysine modification and gene expression orchestrate growth, conidiation and virulence in Beauveria bassiana. Deletion of Rpd3 resulted in severe growth defects on various carbon/nitrogen sources, 97% reduction in conidiation capacity and drastic attenuation in virulence. These phenotypes concurred with differential expression of 1479 proteins and hyperacetylation or hypoacetylation of 2227 lysine residues on 1134 proteins...
March 24, 2018: Environmental Microbiology
Maria G Daskalaki, Christos Tsatsanis, Sotirios C Kampranis
Macrophages respond to noxious stimuli and contribute to inflammatory responses by eliminating pathogens or damaged tissue and maintaining homeostasis. Response to activation signals and maintenance of homeostasis require tight regulation of genes involved in macrophage activation and inactivation processes, as well as genes involved in determining their polarization state. Recent evidence has revealed that such regulation occurs through histone modifications that render inflammatory or polarizing gene promoters accessible to transcriptional complexes...
March 25, 2018: Journal of Cellular Physiology
Danqi Chen, Lei Fang, Hongjie Li, Chunyuan Jin
As the primary metabolite of alcohol and the most abundant carcinogen in tobacco smoke, acetaldehyde is linked to a number of human diseases associated with chronic alcohol consumption and smoking including cancers. In addition to direct DNA damage as a result of the formation of acetaldehyde-DNA adducts, acetaldehyde may also indirectly impact proper genome function through the formation of protein adducts. Histone proteins are the major component of the chromatin. Post-translational histone modifications (PTMs) are critically important for the maintenance of genetic and epigenetic stability...
March 22, 2018: Environmental and Molecular Mutagenesis
Dai Hatakeyama, Masaki Shoji, Seiya Yamayoshi, Rina Yoh, Naho Ohmi, Shiori Takenaka, Ayaka Saitoh, Yumie Arakaki, Aki Masuda, Tsugunori Komatsu, Rina Nagano, Masahiro Nakano, Takeshi Noda, Yoshihiro Kawaoka, Takashi Kuzuhara
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the CREB-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities...
March 19, 2018: Journal of Biological Chemistry
Dinghui Yu, Ying Tan, Molee Chakraborty, Seth Tomchik, Ronald L Davis
The evolutionarily conserved Elongator Complex associates with RNA polymerase II for transcriptional elongation. Elp3 is the catalytic subunit, contains histone acetyltransferase activity, and is associated with neurodegeneration in humans. Elp1 is a scaffolding subunit and when mutated causes familial dysautonomia. Here, we show that elp3 and elp1 are required for aversive long-term olfactory memory in Drosophila RNAi knockdown of elp3 in adult mushroom bodies impairs long-term memory (LTM) without affecting earlier forms of memory...
April 2018: Learning & Memory
Qing Cai, Sen-Miao Tong, Wei Shao, Sheng-Hua Ying, Ming-Guang Feng
Histone acetyltransferases (HATs) and deacetylases (HDACs) maintain dynamics of lysine acetylation/deacetylation on histones and non-histone substrates involved in gene regulation and cellular events. Hos2 is a class I HDAC that deacetylates unique histone H4-K16 site in yeasts. Here, we report that orthologous Hos2 deacetylates H4-K16 and is also involved in the acetylation of histone H3-K56 and the phosphorylation of histone H2A-S129 and cyclin-dependent kinase 1 CDK1-Y15 in Beauveria bassiana, a filamentous fungal insect pathogen...
March 15, 2018: Cellular Microbiology
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