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https://www.readbyqxmd.com/read/28717171/the-aspirin-metabolite-salicylate-inhibits-lysine-acetyltransferases-and-muc1-induced-epithelial-to-mesenchymal-transition
#1
Harvey R Fernandez, Sara K Lindén
MUC1 is a transmembrane mucin that can promote cancer progression, and its upregulation correlates with a worse prognosis in colon cancer. We examined the effects of overexpression of MUC1 in colon cancer cells, finding that it induced epithelial to mesenchymal transition (EMT), including enhanced migration and invasion, and increased Akt phosphorylation. When the clones were treated with the aspirin metabolite salicylate, Akt phosphorylation was decreased and EMT inhibited. As the salicylate motif is necessary for the activity of the lysine acetyltransferase (KAT) inhibitor anacardic acid, we hypothesized these effects were associated with the inhibition of KAT activity...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28714971/budding-yeast-wee1-distinguishes-spindle-pole-bodies-to-guide-their-pattern-of-age-dependent-segregation
#2
Jette Lengefeld, Manuel Hotz, Meaghen Rollins, Kristin Baetz, Yves Barral
Many asymmetrically dividing cells unequally partition cellular structures according to age. Yet, it is unclear how cells differentiate pre-existing from newly synthesized material. Yeast cells segregate the spindle pole body (SPB, centrosome equivalent) inherited from the previous mitosis to the bud, while keeping the new one in the mother cell. Here, we show that the SPB inheritance network (SPIN), comprising the kinases Swe1 (also known as Wee1) and Kin3 (also known as Nek2) and the acetyltransferase NuA4 (also known as Tip60), distinguishes pre-existing from new SPBs...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28710961/epigenetic-modification-differences-between-fetal-fibroblast-cells-and-mesenchymal-stem-cells-of-the-arbas-cashmere-goat
#3
Xiao Wang, Zhimin Wang, Qing Wang, Hefei Wang, Hao Liang, Dongjun Liu
To explore the epigenetic mechanisms regulating mesenchymal stem cells, we analyzed epigenetic patterns in control goat fetal fibroblast cells (gFFCs), adipose-derived stem cells (gADSCs), bone marrow stromal cells (gBMSCs), and muscle-derived satellite cells (gMDSCs). We found that the 5mC content of gBMSC genomes was lower than that of gFFC genomes, while the 5mC content of gADSC and gMDSC genomes surpassed that of gFFC genomes. H3K9 acetylation did not differ significantly among those cells; gFFCs, gADSCs, and gMDSCs contained acetylated H3K9, H3K14, H3K18, H4K5, and H4K12, but gBMSCs contained almost no acetylated H4K5 and H4K12...
July 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28710461/bromodomain-factors-of-bet-family-are-new-essential-actors-of-pericentric-heterochromatin-transcriptional-activation-in-response-to-heat-shock
#4
Edwige Col, Neda Hoghoughi, Solenne Dufour, Jessica Penin, Sivan Koskas, Virginie Faure, Maria Ouzounova, Hector Hernandez-Vargash, Nicolas Reynoird, Sylvain Daujat, Eric Folco, Marc Vigneron, Robert Schneider, André Verdel, Saadi Khochbin, Zdenko Herceg, Cécile Caron, Claire Vourc'h
The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694333/epc1-tip60-mediated-histone-acetylation-facilitates-spermiogenesis-in-mice
#5
Yixin Dong, Kyo-Ichi Isono, Kazuyuki Ohbo, Takaho A Endo, Osamu Ohara, Mamiko Maekawa, Yoshiro Toyama, Chizuru Ito, Kiyotaka Toshimori, Kristian Helin, Narumi Ogonuki, Kimiko Inoue, Atsuo Ogura, Kazutsune Yamagata, Issay Kitabayashi, Haruhiko Koseki
Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian Nucleosome acetyltransferase of H4 (NuA4) complexes, are co-expressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28692054/modeling-cancer-driver-events-in-vitro-using-barrier-bypass-clonal-expansion-assays-and-massively-parallel-sequencing
#6
H Huskova, M Ardin, A Weninger, K Vargova, S Barrin, S Villar, M Olivier, T Stopka, Z Herceg, M Hollstein, J Zavadil, M Korenjak
The information on candidate cancer driver alterations available from public databases is often descriptive and of limited mechanistic insight, which poses difficulties for reliable distinction between true driver and passenger events. To address this challenge, we performed in-depth analysis of whole-exome sequencing data from cell lines generated by a barrier bypass-clonal expansion (BBCE) protocol. The employed strategy is based on carcinogen-driven immortalization of primary mouse embryonic fibroblasts and recapitulates early steps of cell transformation...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28669827/mitochondria-elongation-is-mediated-through-sirt1-mediated-mfn1-stabilization
#7
Nguyen Thi Kim Oanh, Yong-Yea Park, Hyeseong Cho
Mitochondria are highly dynamic organelles that change size and morphology by fusing together or dividing through fission. In response to cellular cues, signaling cascades may post-translationally modify mitochondria-shaping proteins, which lead to a change in mitochondria morphology. Here we show that nicotinamide (NAM), an inhibitor of sirtuin deacetylases, promotes degradation of mitochondria fusion protein mitofusin 1 (MFN1), suggesting that acetylation status of MFN1 is important for its protein stability...
June 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28634400/chronic-treatment-with-cisplatin-induces-chemoresistance-through-the-tip60-mediated-fanconi-anemia-and-homologous-recombination-repair-pathways
#8
Wen-Pin Su, Yen-Chih Ho, Cheng-Kuei Wu, Sen-Huei Hsu, Jia-Lin Shiu, Jheng-Cheng Huang, Song-Bin Chang, Wen-Tai Chiu, Jan-Jong Hung, Tsung-Lin Liu, Wei-Sheng Wu, Pei-Yu Wu, Wu-Chou Su, Jang-Yang Chang, Hungjiun Liaw
The Fanconi anemia pathway in coordination with homologous recombination is essential to repair interstrand crosslinks (ICLs) caused by cisplatin. TIP60 belongs to the MYST family of acetyltransferases and is involved in DNA repair and regulation of gene transcription. Although the physical interaction between the TIP60 and FANCD2 proteins has been identified that is critical for ICL repair, it is still elusive whether TIP60 regulates the expression of FA and HR genes. In this study, we found that the chemoresistant nasopharyngeal carcinoma cells, derived from chronic treatment of cisplatin, show elevated expression of TIP60...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623334/novel-complex-of-hat-protein-tip60-and-nuclear-receptor-pxr-promotes-cell-migration-and-adhesion
#9
Karishma Bakshi, B Ranjitha, Shraddha Dubey, Jaisri Jagannadham, Bharti Jaiswal, Ashish Gupta
PXR is a member of nuclear receptor superfamily and a well-characterized mediator of xenobiotic metabolism. The classical mode of PXR activation involves its binding to appropriate ligand and subsequent heterodimerization with its partner RXR. However, various factors such as post-translational modifications and crosstalk with different cellular factors may also regulate the functional dynamics and behavior of PXR. In the present study, we have identified that TIP60, an essential lysine acetyltransferase protein interacts with unliganded PXR and together this complex promotes cell migration & adhesion...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28546430/cross-talk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#10
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...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#11
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
#12
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...
July 2017: Nature Immunology
https://www.readbyqxmd.com/read/28477118/functional-characterization-of-atm-kinase-using-acetylation-specific-antibodies
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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