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https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#1
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#2
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/28504697/the-transcriptional-coactivator-taz-regulates-reciprocal-differentiation-of-th17-cells-and-treg-cells
#3
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/28477118/functional-characterization-of-atm-kinase-using-acetylation-specific-antibodies
#4
Yingli Sun, Fengxia Du
The activation of ATM is critical in the DNA double strand breaks repair pathway. Acetylation of ATM by Tip60 histone acetyltransferase (HAT) plays a key role in the activation of ATM kinase activity in response to DNA damage. ATM forms a stable complex with Tip60 through the FATC domain of ATM. Tip60 acetylates lysine3016 of ATM, and this acetylation induces the activation of ATM. Several techniques are included in the study of ATM acetylation by Tip60, such as in vitro kinase assay, systematic mutagenesis, western blots...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28445939/epigenetic-therapy-with-inhibitors-of-histone-methylation-suppresses-dna-damage-signaling-and-increases-glioma-cell-radiosensitivity
#5
Ozge Gursoy-Yuzugullu, Chelsea Carman, Rodolfo Bortolozo Serafim, Marios Myronakis, Valeria Valente, Brendan D Price
Radiation therapy is widely used to treat human malignancies, but many tumor types, including gliomas, exhibit significant radioresistance. Radiation therapy creates DNA double-strand breaks (DSBs), and DSB repair is linked to rapid changes in epigenetic modifications, including increased histone methylation. This increased histone methylation recruits DNA repair proteins which can then alter the local chromatin structure and promote repair. Consequently, combining inhibitors of specific histone methyltransferases with radiation therapy may increase tumor radiosensitivity, particularly in tumors with significant therapeutic resistance...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445719/kat-independent-gene-regulation-by-tip60-promotes-esc-self-renewal-but-not-pluripotency
#6
Diwash Acharya, Sarah J Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A Rivera-Pérez, Thomas G Fazzio
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28238654/prmt5-dependent-methylation-of-the-tip60-coactivator-ruvbl1-is-a-key-regulator-of-homologous-recombination
#7
Thomas L Clarke, Maria Pilar Sanchez-Bailon, Kelly Chiang, John J Reynolds, Joaquin Herrero-Ruiz, Tiago M Bandeiras, Pedro M Matias, Sarah L Maslen, J Mark Skehel, Grant S Stewart, Clare C Davies
Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28231279/lysine-acetyltransferase-nua4-and-acetyl-coa-regulate-glucose-deprived-stress-granule-formation-in-saccharomyces-cerevisiae
#8
Meaghen Rollins, Sylvain Huard, Alan Morettin, Jennifer Takuski, Trang Thuy Pham, Morgan D Fullerton, Jocelyn Côté, Kristin Baetz
Eukaryotic cells form stress granules under a variety of stresses, however the signaling pathways regulating their formation remain largely unknown. We have determined that the Saccharomyces cerevisiae lysine acetyltransferase complex NuA4 is required for stress granule formation upon glucose deprivation but not heat stress. Further, the Tip60 complex, the human homolog of the NuA4 complex, is required for stress granule formation in cancer cell lines. Surprisingly, the impact of NuA4 on glucose-deprived stress granule formation is partially mediated through regulation of acetyl-CoA levels, which are elevated in NuA4 mutants...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28196077/enhancer-of-polycomb-coordinates-multiple-signaling-pathways-to-promote-both-cyst-and-germline-stem-cell-differentiation-in-the-drosophila-adult-testis
#9
Lijuan Feng, Zhen Shi, Xin Chen
Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28108589/chromatin-regulation-by-the-nua4-acetyltransferase-complex-is-mediated-by-essential-interactions-between-enhancer-of-polycomb-epl1-and-esa1
#10
Naomi E Searle, Ana Lilia Torres-Machorro, Lorraine Pillus
Enzymes that modify and remodel chromatin act in broadly conserved macromolecular complexes. One key modification is the dynamic acetylation of histones and other chromatin proteins by opposing activities of acetyltransferase and deacetylase complexes. Among acetyltransferases, the NuA4 complex containing Tip60 or its Saccharomyces cerevisiae ortholog Esa1 is of particular significance because of its roles in crucial genomic processes including DNA damage repair and transcription. The catalytic subunit Esa1 is essential, as are five noncatalytic NuA4 subunits...
March 2017: Genetics
https://www.readbyqxmd.com/read/28032867/regulation-of-er-stress-induced-autophagy-by-gsk3%C3%AE-tip60-ulk1-pathway
#11
Tiejian Nie, Shaosong Yang, Hongwei Ma, Lei Zhang, Fangfang Lu, Kai Tao, Ronglin Wang, Ruixin Yang, Lu Huang, Zixu Mao, Qian Yang
Endoplasmic reticulum (ER) stress is involved in many cellular processes. Emerging evidence suggests that ER stress can trigger autophagy; however, the mechanisms by which ER stress regulates autophagy and its role in this condition are not fully understood. HIV Tat-interactive protein, 60 kDa (TIP60) is a newly discovered acetyltransferase that can modulate autophagy flux by activating ULK1 upon growth factor deprivation. In this study, we investigated the mechanisms by which ER stress induces autophagy...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#12
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27899423/myc-mediates-mrna-cap-methylation-of-canonical-wnt-%C3%AE-catenin-signaling-transcripts-by-recruiting-cdk7-and-rna-methyltransferase
#13
Valeriya Posternak, Matthew H Ung, Chao Cheng, Michael D Cole
MYC is a pleiotropic transcription factor that activates and represses a wide range of target genes and is frequently deregulated in human tumors. While much is known about the role of MYC in transcriptional activation and repression, MYC can also regulate mRNA cap methylation through a mechanism that has remained poorly understood. Here, it is reported that MYC enhances mRNA cap methylation of transcripts globally, specifically increasing mRNA cap methylation of genes involved in Wnt/β-catenin signaling. Elevated mRNA cap methylation of Wnt signaling transcripts in response to MYC leads to augmented translational capacity, elevated protein levels, and enhanced Wnt signaling activity...
February 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27814680/ataxia-telangiectasia-mutated-atm-interacts-with-p400-atpase-for-an-efficient-dna-damage-response
#14
Rebecca J Smith, Matthew S Savoian, Lauren E Weber, Jeong Hyeon Park
BACKGROUND: Ataxia telangiectasia mutated (ATM) and TRRAP proteins belong to the phosphatidylinositol 3-kinase-related kinase family and are involved in DNA damage repair and chromatin remodeling. ATM is a checkpoint kinase that is recruited to sites of DNA double-strand breaks where it phosphorylates a diverse range of proteins that are part of the chromatin and DNA repair machinery. As an integral subunit of the TRRAP-TIP60 complexes, p400 ATPase is a chromatin remodeler that is also targeted to DNA double-strand break sites...
November 4, 2016: BMC Molecular Biology
https://www.readbyqxmd.com/read/27798113/oral-facial-digital-syndrome-type-i-cells-exhibit-impaired-dna-repair-unanticipated-consequences-of-defective-ofd1-outside-of-the-cilia-network
#15
Iga Abramowicz, Gillian Carpenter, Mariaevelina Alfieri, Rita Colnaghi, Emily Outwin, Philippe Parent, Christel Thauvin-Robinet, Daniela Iaconis, Brunella Franco, Mark O'Driscoll
Defects in OFD1 underlie the clinically complex ciliopathy, Oral-Facial-Digital syndrome Type I (OFD Type I). Our understanding of the molecular, cellular and clinical consequences of impaired OFD1 originates from its characterised roles at the centrosome/basal body/cilia network. Nonetheless, the first described OFD1 interactors were components of the TIP60 histone acetyltransferase complex. We find that OFD1 can also localise to chromatin and its reduced expression is associated with mis-localization of TIP60 in patient-derived cell lines...
January 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27777629/an-h4k16-histone-acetyltransferase-mediates-decondensation-of-the-x-chromosome-in-c-elegans-males
#16
Alyssa C Lau, Kevin P Zhu, Elizabeth A Brouhard, Michael B Davis, Györgyi Csankovszki
BACKGROUND: In C. elegans, in order to equalize gene expression between the sexes and balance X and autosomal expression, two steps are believed to be required. First, an unknown mechanism is hypothesized to upregulate the X chromosome in both sexes. This mechanism balances the X to autosomal expression in males, but creates X overexpression in hermaphrodites. Therefore, to restore the balance, hermaphrodites downregulate gene expression twofold on both X chromosomes. While many studies have focused on X chromosome downregulation, the mechanism of X upregulation is not known...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27769803/ubiquitin-specific-protease-7-inhibition-impairs-tip60-dependent-foxp3-t-regulatory-cell-function-and-promotes-antitumor-immunity
#17
Liqing Wang, Suresh Kumar, Satinder Dahiya, Feng Wang, Jian Wu, Kheng Newick, Rongxiang Han, Arabinda Samanta, Ulf H Beier, Tatiana Akimova, Tricia R Bhatti, Benjamin Nicholson, Mathew P Kodrasov, Saket Agarwal, David E Sterner, Wei Gu, Joseph Weinstock, Tauseef R Butt, Steven M Albelda, Wayne W Hancock
Foxp3+ T-regulatory (Treg) cells are known to suppress protective host immune responses to a wide variety of solid tumors, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation, e.g. using anti-CTLA-4 monoclonal antibody. Our ongoing studies of the post-translational modifications that regulate Foxp3 demonstrated that the histone/protein acetyltransferase, Tip60, plays a dominant role in promoting acetylation, dimerization and function in Treg cells. We now show that the ubiquitin-specific protease, Usp7, controls Treg function largely by stabilizing the expression and promoting the multimerization of Tip60 and Foxp3...
November 2016: EBioMedicine
https://www.readbyqxmd.com/read/27768769/depletion-of-tip60-from-in-vivo-cardiomyocytes-increases-myocyte-density-followed-by-cardiac-dysfunction-myocyte-fallout-and-lethality
#18
Joseph B Fisher, Audrey Horst, Tina Wan, Min-Su Kim, John Auchampach, John Lough
Tat-interactive protein 60 (Tip60), encoded by the Kat5 gene, is a member of the MYST family of acetyltransferases. Cancer biology studies have shown that Tip60 induces the DNA damage response, apoptosis, and cell-cycle inhibition. Although Tip60 is expressed in the myocardium, its role in cardiomyocytes (CMs) is unclear. Earlier studies here showed that application of cardiac stress to globally targeted Kat5+/-haploinsufficient mice resulted in inhibition of apoptosis and activation of the CM cell-cycle, despite only modest reduction of Tip60 protein levels...
2016: PloS One
https://www.readbyqxmd.com/read/27743347/e3-ligase-uhrf2-stabilizes-the-acetyltransferase-tip60-and-regulates-h3k9ac-and-h3k14ac-via-ring-finger-domain
#19
Shengyuan Zeng, Yangyang Wang, Ting Zhang, Lu Bai, Yalan Wang, Changzhu Duan
UHRF2 is a ubiquitin-protein ligase E3 that regulates cell cycle, genomic stability and epigenetics. We conducted a co-immunoprecipitation assay and found that TIP60 and HDAC1 interact with UHRF2. We previously demonstrated that UHRF2 regulated H3K9ac and H3K14ac differentially in normal and cancer cells. However, the accurate signal transduction mechanisms were not clear. In this study, we found that TIP60 acted downstream of UHRF2 to regulate H3K9ac and H3K14ac expression. TIP60 is stabilized in normal cells by UHRF2 ubiquitination...
March 2017: Protein & Cell
https://www.readbyqxmd.com/read/27688101/the-effect-of-human-papillomavirus-on-dna-repair-in-head-and-neck-squamous-cell-carcinoma
#20
REVIEW
Garren M Low, David S Thylur, Vicky N Yamamoto, Uttam K Sinha
Much of the current literature regarding the molecular pathophysiology of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused on the virus's effect on cell cycle modulation and cell proliferation. A second mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair processes, has been more sparsely studied. The purpose of this review is to describe current understanding about the effect of HPV on DNA repair in HNSCC, taking cues from cervical cancer literature...
October 2016: Oral Oncology
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