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histone acetyltransferase

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https://www.readbyqxmd.com/read/28527406/the-relevance-of-ki-calculation-for-bi-substrate-enzymes-illustrated-by-kinetic-evaluation-of-a-novel-lysine-k-acetyltransferase-8-inhibitor
#1
Hannah Wapenaar, Thea van den Bosch, Niek G J Leus, Petra E van der Wouden, Nikolaos Eleftheriadis, Jos Hermans, Gebremedhin Solomon Hailu, Dante Rotili, Antonello Mai, Alexander Dömling, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets. However, the development of HATi is challenged by the difficulties in kinetic characterization of HAT enzymes and their inhibitors to enable calculation of a reproducible inhibitory potency...
May 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28525378/irf5-is-elevated-in-childhood-onset-sle-and-regulated-by-histone-acetyltransferase-and-histone-deacetylase-inhibitors
#2
Jin Shu, Ling Li, Lan-Bo Zhou, Jun Qian, Zhi-Dan Fan, Li-Li Zhuang, Lu-Lu Wang, Rui Jin, Hai-Guo Yu, Guo-Ping Zhou
Interferon regulatory factor 5 (IRF5) plays a critical role in the induction of type I interferon, proinflammatory cytokines and chemokines, and participates in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). However, the relationship between IRF5 and childhood-onset SLE remains elusive. In the present study, we demonstrated that levels of mRNA expression of IRF5, IFN-α, and Sp1 were significantly increased in childhood-onset SLE, as seen on quantitative real-time PCR, and the expression of Sp1 and IFN-α was positively correlated with IRF5...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524856/histone-variant-h3-3-orchestrates-neural-stem-cell-differentiation-in-the-developing-brain
#3
Wenlong Xia, Jianwei Jiao
During the brain development, the process of neural stem cells (NSCs) proliferation and differentiation is precisely regulated. The deficiency in the embryonic brain development will cause serious developmental disorders. Epigenetic modifications play critical roles in controlling proliferation and differentiation in different types of stem cells. Histone variants, as one of epigenetic regulators, have been reported to be associated with many bioprocesses. Among different variants, H3.3 is one of the important epigenetic regulators, but its role in embryonic NSCs remains unclear...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28523540/rubinstein-taybi-syndrome-and-epigenetic-alterations
#4
Edward Korzus
Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28512251/inhibition-of-the-cell-death-pathway-in-non-alcoholic-steatohepatitis-nash-related-hepatocarcinogenesis-is-associated-with-histone-h4-lysine-16-deacetylation
#5
Aline de Conti, Kostiantyn Dreval, Volodymyr Tryndyak, Orish Ebere Orisakwe, Sharon Ross, Frederick Beland, Igor P Pogribny
Hepatocellular carcinoma (HCC) is one of the most aggressive human cancers and its incidence is steadily increasing worldwide. Recent epidemiological findings have suggested that the increased incidence of HCC is associated with obesity, type 2 diabetes mellitus, and nonalcoholic steatohepatitis (NASH); however, the mechanisms and the molecular pathogenesis of NASH-related HCC are not fully understood. In order to elucidate the underlying mechanisms of the development of NASH-related HCC, we investigated the hepatic transcriptomic and histone modification profiles in Stelic Animal Model (STAM) mice, the first animal model of NASH-related HCC to resemble the disease pathogenesis in humans...
May 16, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#6
Arash Nabbi, Urszula L McClurg, Subhash Thalappilly, Amal Almami, Mahsa Mobahat, Tarek A Bismar, Olivier Binda, Karl T Riabowol
BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development...
May 16, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28510597/ubiquitylation-of-the-acetyltransferase-mof-in-drosophila-melanogaster
#7
Sarah Schunter, Raffaella Villa, Victoria Flynn, Jan B Heidelberger, Anne-Kathrin Classen, Petra Beli, Peter B Becker
The nuclear acetyltransferase MOF (KAT8 in mammals) is a subunit of at least two multi-component complexes involved in transcription regulation. In the context of complexes of the 'Non-Specific-Lethal' (NSL) type it controls transcription initiation of many nuclear housekeeping genes and of mitochondrial genes. While this function is conserved in metazoans, MOF has an additional, specific function in Drosophila in the context of dosage compensation. As a subunit of the male-specific-lethal dosage compensation complex (MSL-DCC) it contributes to the doubling of transcription output from the single male X chromosome by acetylating histone H4...
2017: PloS One
https://www.readbyqxmd.com/read/28506985/histone-acetyltransferase-kat8-is-essential-for-mouse-oocyte-development-by-regulating-ros-levels
#8
Shi Yin, Xiaohua Jiang, Hanwei Jiang, Qian Gao, Fang Wang, Suixing Fan, Teka Khan, Nazish Jabeen, Manan Khan, Asim Ali, Peng Xu, Tej K Pandita, Heng-Yu Fan, Yuanwei Zhang, Qinghua Shi
Proper oocyte development is critical for female fertility and requires timely and accurate control of gene expression. K (Lysine) Acetyltransferase 8 (KAT8), an important component of the X chromosome dosage compensation system in Drosophila, regulates gene activity by acetylating histone H4 preferentially at lysine 16. To explore the function of Kat8 during mouse oocyte development, we crossed Kat8(flox/flox) mice with Gdf9-Cre mice to specifically delete Kat8 in oocytes. Oocyte Kat8 deletion resulted in female infertility with follicle development failure in the secondary and preantral follicle stages...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28504697/the-transcriptional-coactivator-taz-regulates-reciprocal-differentiation-of-th17-cells-and-treg-cells
#9
Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation...
May 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28503202/stabilization-of-foxp3-expression-by-crispr-dcas9-based-epigenome-editing-in-mouse-primary-t-cells
#10
Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa, Akihiko Yoshimura
BACKGROUND: Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context-dependent activity of artificial epigenetic modifier is required. RESULTS: In this study, we applied clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-based epigenome editing to mouse primary T cells, focusing on the Forkhead box P3 (Foxp3) gene locus, a master transcription factor of regulatory T cells (Tregs)...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28500727/biological-function-and-histone-recognition-of-family-iv-bromodomain-containing-proteins
#11
Jonathan T Lloyd, Karen C Glass
Bromodomain proteins function as epigenetic readers that recognize acetylated histone tails to facilitate the transcription of target genes. There are approximately 60 known human bromodomains, which are divided into 8 sub-families based on structural conservation. The bromodomain-containing proteins in family IV include 7 members (BRPF1, BRPF2, BRPF3, BRD7, BRD9, ATAD2 and ATAD2b). The bromodomains of each of these proteins recognize and bind acetyllysine residues on histone tails protruding from the nucleosome...
May 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28499864/role-of-hepatitis-b-core-protein-in-hbv-transcription-and-recruitment-of-histone-acetyltransferases-to-cccdna-minichromosome
#12
Chun Kong Chong, Ching Yan Serene Cheng, Sin Yi Jasmine Tsoi, Fung-Yu Huang, Fen Liu, Wai-Kay Seto, Ching-Lung Lai, Man-Fung Yuen, Danny Ka-Ho Wong
The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured...
May 10, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28497301/various-regulatory-modes-for-circadian-rhythmicity-and-sexual-dimorphism-in-the-non-neuronal-cardiac-cholinergic-system
#13
Shino Oikawa, Yuko Kai, Asuka Mano, Hisayuki Ohata, Takahiro Nemoto, Yoshihiko Kakinuma
Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern...
May 11, 2017: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/28496451/genome-wide-identification-of-histone-modifiers-and-their-expression-patterns-during-fruit-abscission-in-litchi
#14
Manjun Peng, Peiyuan Ying, Xuncheng Liu, Caiqin Li, Rui Xia, Jianguo Li, Minglei Zhao
Modifications to histones, including acetylation and methylation processes, play crucial roles in the regulation of gene expression in plant development as well as in stress responses. However, limited information on the enzymes catalyzing histone acetylation and methylation in non-model plants is currently available. In this study, several histone modifier (HM) types, including six histone acetyltransferases (HATs), 11 histone deacetylases (HDACs), 48 histone methyltransferases (HMTs), and 22 histone demethylases (HDMs), are identified in litchi (Litchi chinensis Sonn...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28496102/partial-microduplication-in-the-histone-acetyltransferase-complex-member-kansl1-is-associated-with-congenital-heart-defects-in-22q11-2-microdeletion-syndrome-patients
#15
Luis E León, Felipe Benavides, Karena Espinoza, Cecilia Vial, Patricia Alvarez, Mirta Palomares, Guillermo Lay-Son, Macarena Miranda, Gabriela M Repetto
22q11.2 microdeletion syndrome (22q11.2DS) is the most common microdeletion disorder in humans, with an incidence of 1/4000 live births. It is caused by a heterozygous deletion of 1.5-3 Mb on chromosome region 22q11.2. Patients with the deletion present features that include neuropsychiatric problems, craniofacial abnormalities and cardiovascular malformations. However, the phenotype is highly variable and the factors related to the clinical heterogeneity are not fully understood. About 65% of patients with 22q11...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28496053/chemical-and-structural-biology-of-protein-lysine-deacetylases
#16
Minoru Yoshida, Norio Kudo, Saori Kosono, Akihiro Ito
Histone acetylation is a reversible posttranslational modification that plays a fundamental role in regulating eukaryotic gene expression and chromatin structure/function. Key enzymes for removing acetyl groups from histones are metal (zinc)-dependent and NAD(+)-dependent histone deacetylases (HDACs). The molecular function of HDACs have been extensively characterized by various approaches including chemical, molecular, and structural biology, which demonstrated that HDACs regulate cell proliferation, differentiation, and metabolic homeostasis, and that their alterations are deeply involved in various human disorders including cancer...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28488757/stimulation-of-pol-iii-dependent-5s-rrna-and-u6-snrna-gene-expression-by-ap-1-transcription-factors
#17
Richa Ahuja, Vijay Kumar
RNA polymerase III transcribes structurally diverse group of essential non-coding RNAs including 5S rRNA and U6 snRNA. These non-coding RNAs are involved in RNA processing and ribosome biogenesis, thus, coupling Pol III activity to the rate of protein synthesis, cell growth and proliferation. Even though a few Pol II-associated transcription factors have been reported to participate in Pol III-dependent transcription, its activation by AP-1 factors c-Fos and c-Jun has remained unexplored. Here, we show that c-Fos and c-Jun bind to specific sites in the regulatory regions of 5S rRNA (type I) and U6 snRNA (type III) gene promoters and stimulate their transcription...
May 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28487409/rice-homeodomain-protein-wox11-recruits-a-histone-acetyltransferase-complex-to-establish-programs-of-cell-proliferation-of-crown-root-meristem
#18
Shaoli Zhou, Wei Jiang, Fei Long, Saifeng Cheng, Wenjing Yang, Yu Zhao, Dao-Xiu Zhou
Shoot-borne crown roots are the major root system in cereals. Previous work has shown that the Wuschel-related homeobox gene WOX11 is necessary and sufficient to promote rice (Oryza sativa) crown root emergence and elongation. Here, we show that WOX11 recruits the ADA2-GCN5 histone acetyltransferase (HAT) module to activate downstream target genes in crown root meristem. Rice ADA2 and GCN5 genes are highly expressed in root meristem and are shown to be essential for cell division and growth. WOX11 and ADA2-GCN5 commonly target and regulate a set of root-specific genes involved in energy metabolism, cell wall biosynthesis, and hormone response, some of which are known to be important for root development...
May 9, 2017: Plant Cell
https://www.readbyqxmd.com/read/28486547/hat2-mediates-histone-h4k4-acetylation-and-affects-micrococcal-nuclease-sensitivity-of-chromatin-in-leishmania-donovani
#19
Pravin K Jha, Mohd Imran Khan, Anshul Mishra, Pradeep Das, Kislay K Sinha
Histone post-translational modifications (PTMs) such as acetylation and methylation are known to affect chromatin higher order structures. Primary targets of these modifications include basic residues present at N-terminus tail region of core histones. Four histone acetyltransferase (HAT) genes have been identified in trypanosomatids. HAT1, HAT3 and HAT4 of Leishmania donovani have been partially characterized. However, there is no report about HAT2 of Leishmania donovani. Lysine residues present on the N-terminal tail of Leishmania donovani histone H4 are conserved in other trypanosomatids and humans...
2017: PloS One
https://www.readbyqxmd.com/read/28485815/somatic-mutation-profiles-of-clear-cell-endometrial-tumors-revealed-by-whole-exome-and-targeted-gene-sequencing
#20
Matthieu Le Gallo, Meghan L Rudd, Mary Ellen Urick, Nancy F Hansen, Suiyuan Zhang, Fred Lozy, Dennis C Sgroi, August Vidal Bel, Xavier Matias-Guiu, Russell R Broaddus, Karen H Lu, Douglas A Levine, David G Mutch, Paul J Goodfellow, Helga B Salvesen, James C Mullikin, Daphne W Bell
BACKGROUND: The molecular pathogenesis of clear cell endometrial cancer (CCEC), a tumor type with a relatively unfavorable prognosis, is not well defined. We searched exome-wide for novel somatically mutated genes in CCEC and assessed the mutational spectrum of known and candidate driver genes in a large cohort of cases. METHODS: We conducted whole exome sequencing of paired tumor-normal DNAs from 16 cases of CCEC (12 CCECs and the CCEC components of 4 mixed histology tumors)...
May 9, 2017: Cancer
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