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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
Anna Greißel, Mihaela Culmes, Rainer Burgkart, Alexander Zimmermann, Hans-Henning Eckstein, Alma Zernecke, Jaroslav Pelisek
BACKGROUND: The aim of the study was to analyze histone acetylation, methylation, and the expression of their corresponding transferases in atherosclerotic plaques of patients with carotid artery stenosis. METHODS: Atherosclerotic tissue from our biobank (n=80) was divided into various segments covering all plaque stages and classified according to the American Heart Association. The plaques were assigned to early (types I-III) or advanced (types V-VII) stage group of atherosclerosis...
March 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Federica Franciosi, Ghylene Goudet, Irene Tessaro, Pascal Papillier, Rozenn Dalbies-Tran, Fabrice Reigner, Stefan Deleuze, Cecile Douet, Ileana Miclea, Valentina Lodde, Alberto M Luciano
Implantation failure and genetic developmental disabilities in mammals are caused by errors in chromosome segregation originating mainly in the oocyte during meiosis I. Some conditions, like maternal ageing or in vitro maturation (IVM), increase the incidence of oocyte aneuploidy. Here oocytes from adult mares were used to investigate oocyte maturation in a monovulatory species. Experiments were conducted to compare: (1) the incidence of aneuploidy, (2) the morphology of the spindle, (3) the acetylation of lysine 16 on histone H4 (H4K16) and (4) the relative amount of histone acetyltransferase 1 (HAT1), K(lysine) acetyltransferase 8 (KAT8, also known as MYST1), histone deacetylase 1 (HDAC1) and NAD-dependent protein deacetylase sirtuin 1 (SIRT1) mRNA in metaphase II stage oocytes that were in vitro matured or collected from peri-ovulatory follicles...
December 14, 2015: Reproduction, Fertility, and Development
B N Sheikh, W Bechtel-Walz, J Lucci, O Karpiuk, I Hild, B Hartleben, J Vornweg, M Helmstädter, A H Sahyoun, V Bhardwaj, T Stehle, S Diehl, O Kretz, A K Voss, T Thomas, T Manke, T B Huber, A Akhtar
MOF (MYST1, KAT8) is the major H4K16 lysine acetyltransferase (KAT) in Drosophila and mammals and is essential for embryonic development. However, little is known regarding the role of MOF in specific cell lineages. Here we analyze the differential role of MOF in proliferating and terminally differentiated tissues at steady state and under stress conditions. In proliferating cells, MOF directly binds and maintains the expression of genes required for cell cycle progression. In contrast, MOF is dispensable for terminally differentiated, postmitotic glomerular podocytes under physiological conditions...
May 2016: Oncogene
Antoine Huguet, Aurélie Hatton, Romain Villot, Hélène Quenault, Yannick Blanchard, Valérie Fessard
Cylindrospermopsin (CYN) is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs) using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes), and DNA recombination and repair (with up-regulation of aptx and pms2 genes)...
2014: PloS One
Tomasz Chelmicki, Friederike Dündar, Matthew James Turley, Tasneem Khanam, Tugce Aktas, Fidel Ramírez, Anne-Valerie Gendrel, Patrick Rudolf Wright, Pavankumar Videm, Rolf Backofen, Edith Heard, Thomas Manke, Asifa Akhtar
Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA...
2014: ELife
Anbalagan Jaganathan, Pratima Chaurasia, Guang-Qian Xiao, Marc Philizaire, Xiang Lv, Shen Yao, Kerry L Burnstein, De-Pei Liu, Alice C Levine, Shiraz Mujtaba
In prostate cancer (PCa), the functional synergy between androgen receptor (AR) and nuclear factor-κ B (NF-κB) escalates the resistance to therapeutic regimens and promotes aggressive tumor growth. Although the underlying mechanisms are less clear, gene regulatory abilities of coactivators can bridge the transcription functions of AR and NF-κB. The present study shows that MYST1 (MOZ, YBF2 and SAS2, and TIP60 protein 1) costimulates AR and NF-κB functions in PCa cells. We demonstrate that activation of NF-κB promotes deacetylation of MYST1 by sirtuin 1...
June 2014: Molecular Endocrinology
Sui Sheng T Hua, John J Beck, Siov Bouy L Sarreal, Wai Gee
Aspergillus flavus is a ubiquitous saprophyte that is able to produce the most potent natural carcinogenic compound known as aflatoxin B1 (AFB1). This toxin frequently contaminates crops including corn, cotton, peanuts, and tree nuts causing substantial economic loss worldwide. Consequently, more than 100 countries have strict regulations limiting AFB1 in foodstuffs and feedstuffs. Plants and microbes are able to produce volatile compounds that act as a defense mechanism against other organisms. Pichia anomala strain WRL-076 is a biocontrol yeast currently being tested to reduce AF contamination of tree nuts in California...
May 2014: Mycotoxin Research
Xiaoming Zhao, Jiaming Su, Fei Wang, Da Liu, Jian Ding, Yang Yang, Joan W Conaway, Ronald C Conaway, Lingling Cao, Donglu Wu, Min Wu, Yong Cai, Jingji Jin
hMOF (MYST1), a histone acetyltransferase (HAT), forms at least two distinct multiprotein complexes in human cells. The male specific lethal (MSL) HAT complex plays a key role in dosage compensation in Drosophila and is responsible for histone H4K16ac in vivo. We and others previously described a second hMOF-containing HAT complex, the non-specific lethal (NSL) HAT complex. The NSL complex has a broader substrate specificity, can acetylate H4 on K16, K5, and K8. The WD (tryptophan-aspartate) repeat domain 5 (WDR5) and host cell factor 1 (HCF1) are shared among members of the MLL/SET (mixed-lineage leukemia/set-domain containing) family of histone H3K4 methyltransferase complexes...
November 2013: PLoS Genetics
Riccardo Giampieri, Mario Scartozzi, Cristian Loretelli, Francesco Piva, Alessandra Mandolesi, Giovanni Lezoche, Michela Del Prete, Alessandro Bittoni, Luca Faloppi, Maristella Bianconi, Luca Cecchini, Mario Guerrieri, Italo Bearzi, Stefano Cascinu
Clinical data indicate that prognostic stratification of radically resected colorectal cancer based on disease stage only may not be always be adequate. Preclinical findings suggest that cancer stem cells may influence the biological behaviour of colorectal cancer independently from stage: objective of the study was to assess whether a panel of stemness markers were correlated with clinical outcome in resected stage II and III colon cancer patients. A panel of 66 markers of stemness were analysed and thus patients were divided into two groups (A and B) with most patients clustering in a manner consistent with different time to relapse by using a statistical algorithm...
2013: PloS One
Jens Füllgrabe, Melinda A Lynch-Day, Nina Heldring, Wenbo Li, Robert B Struijk, Qi Ma, Ola Hermanson, Michael G Rosenfeld, Daniel J Klionsky, Bertrand Joseph
Autophagy is an evolutionarily conserved catabolic process involved in several physiological and pathological processes. Although primarily cytoprotective, autophagy can also contribute to cell death; it is thus important to understand what distinguishes the life or death decision in autophagic cells. Here we report that induction of autophagy is coupled to reduction of histone H4 lysine 16 acetylation (H4K16ac) through downregulation of the histone acetyltransferase hMOF (also called KAT8 or MYST1), and demonstrate that this histone modification regulates the outcome of autophagy...
August 22, 2013: Nature
Yong Wang, Rui Zhang, Donglu Wu, Zhihua Lu, Wentao Sun, Yong Cai, Chunxi Wang, Jingji Jin
BACKGROUND: MYST1 (also known as hMOF), a member of the MYST family of histone acetyltransferases (HATs) as an epigenetic mark of active genes, is mainly responsible for histone H4K16 acetylation in the cells. Recent studies have shown that the abnormal gene expression of hMOF is involved in certain primary cancers. Here we examined the involvement of hMOF expression and histone H4K16 acetylation in primary renal cell carcinoma (RCC). Simultaneously, we investigated the correlation between the expression of hMOF and clear cell RCC (ccRCC) biomarker carbohydrase IX (CA9) in RCC...
2013: Journal of Experimental & Clinical Cancer Research: CR
Blandine Patillon, Pierre Luisi, Hélène Blanché, Etienne Patin, Howard M Cann, Emmanuelle Génin, Audrey Sabbagh
VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2) is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK). This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus...
2012: PloS One
Hua Yuan, Dorine Rossetto, Hestia Mellert, Weiwei Dang, Madhusudan Srinivasan, Jamel Johnson, Santosh Hodawadekar, Emily C Ding, Kaye Speicher, Nebiyu Abshiru, Rocco Perry, Jiang Wu, Chao Yang, Y George Zheng, David W Speicher, Pierre Thibault, Alain Verreault, F Bradley Johnson, Shelley L Berger, Rolf Sternglanz, Steven B McMahon, Jacques Côté, Ronen Marmorstein
The MYST protein lysine acetyltransferases are evolutionarily conserved throughout eukaryotes and acetylate proteins to regulate diverse biological processes including gene regulation, DNA repair, cell-cycle regulation, stem cell homeostasis and development. Here, we demonstrate that MYST protein acetyltransferase activity requires active site lysine autoacetylation. The X-ray crystal structures of yeast Esa1 (yEsa1/KAT5) bound to a bisubstrate H4K16CoA inhibitor and human MOF (hMOF/KAT8/MYST1) reveal that they are autoacetylated at a strictly conserved lysine residue in MYST proteins (yEsa1-K262 and hMOF-K274) in the enzyme active site...
January 4, 2012: EMBO Journal
Feixia Chu, Xuefeng Ren, Amanda Chasse, Taylor Hickman, Luoping Zhang, Jessica Yuh, Martyn T Smith, Alma L Burlingame
Recent studies reveal that posttranslational modifications on chromatin proteins, especially histones, organize genomic DNA and mediate various cellular responses to environmental influences. Quantitative mass spectrometric analysis is a powerful approach to reveal these dynamic events on chromatin in a systematic manner. Here, the effects of arsenic exposure on histone epigenetic state were investigated in human UROtsa cells, and a reduction in acetylation level on several histone H3 and H4 lysine residues was detected...
June 30, 2011: Chemico-biological Interactions
Xiangzhi Li, Callie Ann Sprunger Corsa, Patricia W Pan, Lipeng Wu, David Ferguson, Xiaochun Yu, Jinrong Min, Yali Dou
MOF (MYST1) is the major enzyme to catalyze acetylation of histone H4 lysine 16 (K16) and is highly conserved through evolution. Using a conditional knockout mouse model and the derived mouse embryonic fibroblast cell lines, we showed that loss of Mof led to a global reduction of H4 K16 acetylation, severe G(2)/M cell cycle arrest, massive chromosome aberration, and defects in ionizing radiation-induced DNA damage repair. We further showed that although early DNA damage sensing and signaling by ATM were normal in Mof-null cells, the recruitment of repair mediator protein Mdc1 and its downstream signaling proteins 53bp1 and Brca1 to DNA damage foci was completely abolished...
November 2010: Molecular and Cellular Biology
Yong Cai, Jingji Jin, Selene K Swanson, Michael D Cole, Seung Hyuk Choi, Laurence Florens, Michael P Washburn, Joan W Conaway, Ronald C Conaway
Human MOF (MYST1), a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs), is the human ortholog of the Drosophila males absent on the first (MOF) protein. MOF is the catalytic subunit of the male-specific lethal (MSL) HAT complex, which plays a key role in dosage compensation in the fly and is responsible for a large fraction of histone H4 lysine 16 (H4K16) acetylation in vivo. MOF was recently reported to be a component of a second HAT complex, designated the non-specific lethal (NSL) complex (Mendjan, S...
February 12, 2010: Journal of Biological Chemistry
Hestia S Mellert, Steven B McMahon
Dynamic lysine acetylation regulates proteins involved in diverse cellular processes, with individual enzymes often acetylating multiple substrates. Here, Li et al. (2009) show that the substrate specificity of hMOF/MYST1/KAT8 is controlled by differential interaction with two mutually exclusive partners.
October 23, 2009: Molecular Cell
William Jaime Jo, Xuefeng Ren, Feixia Chu, Maria Aleshin, Henri Wintz, Alma Burlingame, Martyn Thomas Smith, Chris Dillon Vulpe, Luoping Zhang
Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As(III)). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As(III) through the modulation of chromatin state...
December 15, 2009: Toxicology and Applied Pharmacology
R I Dmitriev, M I Shakhparonov, N B Pestov
The major function of protein MYST1 is acetylation of histone H4 at the K16 residue. This modification is essential for chromatin remodeling and is used for regulation of gene expression in eukaryotes. MYST1 is a part of multiprotein complexes that accomplish functions of male X-chromosome activation and thereby functions of dosage compensation in drosophila and, in mammals, global acetylation of histone H4 K16. Recently, novel functional links between MYST1 and proteins ATM and p53 have been observed, and it is recognized that MYST1 plays a role in tumor suppression mechanisms...
August 2008: Biochemistry. Biokhimii︠a︡
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