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Matthew S Yan, Paul J Turgeon, Hon Sum Jeffrey Man, Michelle K Dubinsky, Jr Jyun David Ho, Suzan El-Rass, You-Dong Wang, Xiao-Yan Wen, Philip A Marsden
Although the functional role of chromatin marks at promoters in mediating cell-restricted gene expression has been well characterized, the role of intragenic chromatin marks is not well understood, especially in endothelial cell (EC) gene expression. Here, we characterized the histone H3 and H4 acetylation profiles of 19 genes with EC-enriched expression via loci-wide chromatin immunoprecipitation followed by ultra high resolution (5 bp) tiling array analysis in ECs versus non-ECs throughout their genomic loci...
February 6, 2018: Journal of Biological Chemistry
Chengmei Xie, Hongyan Shen, Hui Zhang, Jinting Yan, Yang Liu, Fuwen Yao, Xi Wang, Zhongyi Cheng, Tie-Shan Tang, Caixia Guo
Environmental stresses are important factors causing male infertility which attracts broad attention. Protein acetylation is a pivotal post-translational modification and modulates diverse physiological processes including spermatogenesis. In this study, we employed quantitative proteomic techniques and bioinformatics tools to analyze the alterations of acetylome profile of mouse testis after heat shock and X-irradiation. Overall, we identified 1139 lysine acetylation sites in 587 proteins in which 1020 lysine acetylation sites were quantified...
March 2018: Biochimica et Biophysica Acta
Mercedes Pardo, Lu Yu, Shihpei Shen, Peri Tate, Daniel Bode, Blake L Letney, Dawn E Quelle, William Skarnes, Jyoti S Choudhary
MYST histone acetyltransferases have crucial functions in transcription, replication and DNA repair and are hence implicated in development and cancer. Here we characterise Myst2/Kat7/Hbo1 protein interactions in mouse embryonic stem cells by affinity purification coupled to mass spectrometry. This study confirms that in embryonic stem cells Myst2 is part of H3 and H4 histone acetylation complexes similar to those described in somatic cells. We identify a novel Myst2-associated protein, the tumour suppressor protein Niam (Nuclear Interactor of ARF and Mdm2)...
August 15, 2017: Scientific Reports
Masayoshi Iizuka, Takao Susa, Mimi Tamamori-Adachi, Hiroko Okinaga, Tomoki Okazaki
Estrogen receptors (ER) are important transcription factors to relay signals from estrogen and to regulate proliferation of some of breast cancers. The cycling of estrogen-induced DNA binding and ubiquitin-linked proteolysis of ER potentiates ER-mediated transcription. Indeed, several transcriptional coactivators for ER-dependent transcription ubiquitinate ER. Histone acetyltransferase (HAT) Hbo1/KAT7/MYST2, involved in global histone acetylation, DNA replication, transcription, and cellular proliferation, promotes proteasome-dependent degradation of ERα through ubiquitination...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Shouda Gao, Xiangbei Qi, Junke Li, Linchao Sang
Rheumatoid arthritis (RA) is a chronic autoimmune disease involving multiple cellular participants, of which synovial fibroblasts (SFs) are tightly connected with the development and progression of RA. Here, we provide evidence confirming that KAT7, an H4-specific histone acetylase, is upregulated in SFs of RA patients, which is at least attributed to the stimulation by RA-associated proinflammatory cytokines, such as TNF-α, IL-1β or IFN-γ. In addition, KAT7 overexpression in cultured human fibroblast-like synoviocytes (HFLSs) induces IL-6 and TGF-β expression through an epigenetic mechanism, and in vitro T helper 17 (Th17) cell polarization cultured in these supernatants shows promoted cell differentiation...
July 22, 2017: Biochemical and Biophysical Research Communications
Dane M Newman, Anne K Voss, Tim Thomas, Rhys S Allan
Histone acetylation has an important role in gene regulation, DNA replication, and repair. Because these processes are central to the development of the immune system, we investigated the role of a previously unstudied histone acetyltransferase named KAT7 (also known as Myst2 or HBO1) in the regulation of thymopoiesis and observed a critical role in the regulation of conventional and innate-like T cell development. We found that KAT7-deficient thymocytes displayed normal, positive selection and development into mature single-positive αβ thymocytes; however, we observed few peripheral CD4+ or CD8+ T cells...
April 2017: Journal of Leukocyte Biology
A V Raevsky, M Sharifi, D A Samofalova, P A Karpov, Y B Blume
Histone lysine acetylation is a reversible post-translational modification that does not involve changes in DNA sequences. Enzymes play an important role in developmental processes and their deregulation has been linked to the progression of diverse disorders. The HAT enzyme family fulfills an important role in various developmental processes mediated by the state of chromatin, and have been attributed to its deregulation. To understand acetylation mechanisms and their role in cell signaling, transcriptional regulation, and apoptosis, it is crucial to identify and analyze acetylation sites...
November 2016: Journal of Molecular Modeling
Linya You, Lin Li, Jinfeng Zou, Kezhi Yan, Jad Belle, Anastasia Nijnik, Edwin Wang, Xiang-Jiao Yang
Hematopoietic stem cells (HSCs) serve as a life-long reservoir for all blood cell types and are clinically useful for a variety of HSC transplantation-based therapies. Understanding the role of chromatin organization and regulation in HSC homeostasis may provide important insights into HSC development. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multivalent chromatin regulator that possesses 4 nucleosome-binding domains and activates 3 lysine acetyltransferases (KAT6A, KAT6B, and KAT7), suggesting that this protein has the potential to stimulate crosstalk between different chromatin modifications...
September 1, 2016: Journal of Clinical Investigation
Jun-Ichirou Ohzeki, Nobuaki Shono, Koichiro Otake, Nuno M C Martins, Kazuto Kugou, Hiroshi Kimura, Takahiro Nagase, Vladimir Larionov, William C Earnshaw, Hiroshi Masumoto
Centromere chromatin containing histone H3 variant CENP-A is required for accurate chromosome segregation as a foundation for kinetochore assembly. Human centromere chromatin assembles on a part of the long α-satellite (alphoid) DNA array, where it is flanked by pericentric heterochromatin. Heterochromatin spreads into adjacent chromatin and represses gene expression, and it can antagonize centromere function or CENP-A assembly. Here, we demonstrate an interaction between CENP-A assembly factor M18BP1 and acetyltransferase KAT7/HBO1/MYST2...
June 6, 2016: Developmental Cell
Jason Palladino, Barbara G Mellone
Heterochromatin is incompatible with centromeric chromatin assembly and propagation. In this issue of Developmental Cell, Ohzeki et al. (2016) reveal that a critical role of the Mis18 complex is to transiently recruit the lysine acetyltransferase KAT7 to centromeres to facilitate the removal of H3K9me3 and the deposition of CENP-A.
June 6, 2016: Developmental Cell
Yanshuo Han, Fadwa Tanios, Christian Reeps, Jian Zhang, Kristina Schwamborn, Hans-Henning Eckstein, Alma Zernecke, Jaroslav Pelisek
BACKGROUND: Epigenetic modifications may play a relevant role in the pathogenesis of human abdominal aortic aneurysm (AAA). The aim of the study was therefore to investigate histone acetylation and expression of corresponding lysine [K] histone acetyltransferases (KATs) in AAA. RESULTS: A comparative study of AAA tissue samples (n = 37, open surgical intervention) and healthy aortae (n = 12, trauma surgery) was performed using quantitative PCR, immunohistochemistry (IHC), and Western blot...
2016: Clinical Epigenetics
Virendra Singh, Laishram C Singh, Avninder P Singh, Jagannath Sharma, Bibhuti B Borthakur, Arundhati Debnath, Avdhesh K Rai, Rup K Phukan, Jagadish Mahanta, Amal C Kataki, Sujala Kapur, Sunita Saxena
Esophageal cancer incidence is reported in high frequency in northeast India. The etiology is different from other population at India due to wide variations in dietary habits or nutritional factors, tobacco/betel quid chewing and alcohol habits. Since DNA methylation, histone modification and miRNA-mediated epigenetic processes alter the gene expression, the involvement of these processes might be useful to find out epigenetic markers of esophageal cancer risk in northeast Indian population. The present investigation was aimed to carryout differential expression profiling of chromatin modification enzymes in tumor and normal tissue collected from esophageal squamous cell carcinoma (ESCC) patients...
2015: American Journal of Cancer Research
Linya You, Kezhi Yan, Jinfeng Zou, Hong Zhao, Nicholas R Bertos, Morag Park, Edwin Wang, Xiang-Jiao Yang
With hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain- and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity...
May 1, 2015: Journal of Biological Chemistry
Linya You, Kezhi Yan, Jinfeng Zou, Jinfeng Zhou, Hong Zhao, Nicholas R Bertos, Morag Park, Edwin Wang, Xiang-Jiao Yang
Lysine acetylation has recently emerged as an important post-translational modification in diverse organisms, but relatively little is known about its roles in mammalian development and stem cells. Bromodomain- and PHD finger-containing protein 1 (BRPF1) is a multidomain histone binder and a master activator of three lysine acetyltransferases, MOZ, MORF and HBO1, which are also known as KAT6A, KAT6B and KAT7, respectively. While the MOZ and MORF genes are rearranged in leukemia, the MORF gene is also mutated in prostate and other cancers and in four genetic disorders with intellectual disability...
March 2015: PLoS Genetics
Linya You, Jinfeng Zou, Hong Zhao, Nicholas R Bertos, Morag Park, Edwin Wang, Xiang-Jiao Yang
Epigenetic mechanisms are important in different neurological disorders, and one such mechanism is histone acetylation. The multivalent chromatin regulator BRPF1 (bromodomain- and plant homeodomain-linked (PHD) zinc finger-containing protein 1) recognizes different epigenetic marks and activates three histone acetyltransferases, so it is both a reader and a co-writer of the epigenetic language. The three histone acetyltransferases are MOZ, MORF, and HBO1, which are also known as lysine acetyltransferase 6A (KAT6A), KAT6B, and KAT7, respectively...
March 13, 2015: Journal of Biological Chemistry
Heng Yang, Christie E Pinello, Jian Luo, Dawei Li, Yunfei Wang, Lisa Y Zhao, Stephan C Jahn, Sanjay Adrian Saldanha, Peter Chase, Jamie Planck, Kyla R Geary, Haiching Ma, Brian K Law, William R Roush, Peter Hodder, Daiqing Liao
Acetyltransferase p300 (KAT3B) plays key roles in signaling cascades that support cancer cell survival and sustained proliferation. Thus, p300 represents a potential anticancer therapeutic target. To discover novel anticancer agents that target p300, we conducted a high-throughput screening campaign. A library of 622,079 compounds was assayed for cytotoxicity to the triple-negative breast cancer (TNBC) cell line MDA-MB-231 but not to the human mammary epithelial cells. The resulting compounds were tested in a biochemical assay for inhibiting the enzymatic activity of p300...
May 2013: Molecular Cancer Therapeutics
B Kahali, S J B Gramling, S B Marquez, K Thompson, L Lu, D Reisman
Brahma (BRM) is a novel anticancer gene, which is frequently inactivated in a variety of tumor types. Unlike many anticancer genes, BRM is not mutated, but rather epigenetically silenced. In addition, histone deacetylase complex (HDAC) inhibitors are known to reverse BRM silencing, but they also inactivate it via acetylation of its C-terminus. High-throughput screening has uncovered many compounds that are effective at pharmacologically restoring BRM and thereby inhibit cancer cell growth. As we do not know which specific proteins, if any, regulate BRM, we sought to identify the proteins, which underlie the epigenetic suppression of BRM...
January 30, 2014: Oncogene
Andrew J Kueh, Mathew P Dixon, Anne K Voss, Tim Thomas
We report here that the MYST histone acetyltransferase HBO1 (histone acetyltransferase bound to ORC; MYST2/KAT7) is essential for postgastrulation mammalian development. Lack of HBO1 led to a more than 90% reduction of histone 3 lysine 14 (H3K14) acetylation, whereas no reduction of acetylation was detected at other histone residues. The decrease in H3K14 acetylation was accompanied by a decrease in expression of the majority of genes studied. However, some genes, in particular genes regulating embryonic patterning, were more severely affected than "housekeeping" genes...
February 2011: Molecular and Cellular Biology
Rebecca E Schweppe, Joshua P Klopper, Christopher Korch, Umarani Pugazhenthi, Miriam Benezra, Jeffrey A Knauf, James A Fagin, Laura A Marlow, John A Copland, Robert C Smallridge, Bryan R Haugen
CONTEXT: Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up to 36% of cell lines are cross- contaminated. OBJECTIVE: We evaluated 40 reported thyroid cancer-derived cell lines using short tandem repeat and single nucleotide polymorphism array analysis. RESULTS: Only 23 of 40 cell lines tested have unique genetic profiles. The following groups of cell lines are likely derivatives of the same cell line: BHP5-16, BHP17-10, BHP14-9, and NPA87; BHP2-7, BHP10-3, BHP7-13, and TPC1; KAT5, KAT10, KAT4, KAT7, KAT50, KAK1, ARO81-1, and MRO87-1; and K1 and K2...
November 2008: Journal of Clinical Endocrinology and Metabolism
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