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https://www.readbyqxmd.com/read/27890611/histone-methyltransferase-setdb1-is-indispensable-for-meckel-s-cartilage-development
#1
Kohei Yahiro, Norihisa Higashihori, Keiji Moriyama
The histone methyltransferase Setdb1 represses gene expression by catalyzing lysine 9 of histone H3 trimethylation. Given that the conventional knockout of Setdb1 is embryo-lethal at the implantation stage, its role in craniofacial development is poorly understood. Here, we investigated the role of Setdb1, using conditional knockout mice-in which Setdb1 was deleted in the Meckel's cartilage (Setdb1 CKO)-and the mouse chondrogenic cell line ATDC5-in which Setdb1 was inhibited by siRNA. Deletion of Setdb1 in Meckel's cartilage, the supportive tissue in the embryonic mandible, led to its enlargement, instead of the degeneration that normally occurs...
November 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27867535/erratum-canonical-wnt-signalling-regulates-nuclear-export-of-setdb1-during-skeletal-muscle-terminal-differentiation
#2
Sophie Beyer, Julien Pontis, Elija Schirwis, Valentine Battisti, Anja Rudolf, Fabien Le Grand, Slimane Ait-Si-Ali
[This corrects the article DOI: 10.1038/celldisc.2016.37.].
2016: Cell Discovery
https://www.readbyqxmd.com/read/27798683/ubiquitination-of-lysine-867-of-the-human-setdb1-protein-upregulates-its-histone-h3-lysine-9-h3k9-methyltransferase-activity
#3
Kenji Ishimoto, Natsuko Kawamata, Yoshie Uchihara, Moeka Okubo, Reiko Fujimoto, Eiko Gotoh, Keisuke Kakinouchi, Eiichi Mizohata, Nobumasa Hino, Yoshiaki Okada, Yasuhiro Mochizuki, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Tsuyoshi Inoue, Keisuke Tachibana, Takefumi Doi
Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1...
2016: PloS One
https://www.readbyqxmd.com/read/27795446/transcriptional-silencing-of-moloney-murine-leukemia-virus-in-human-embryonic-carcinoma-cells
#4
Gary Z Wang, Stephen P Goff
: Embryonic carcinoma (EC) cells are malignant counterparts of embryonic stem (ES) cells and serve as useful models for investigating cellular differentiation and human embryogenesis. Though the susceptibility of murine EC cells to retroviral infection has been extensively analyzed, few studies of retrovirus infection of human EC cells have been performed. We tested the susceptibility of human EC cells to transduction by retroviral vectors derived from three different retroviral genera...
October 26, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27790377/canonical-wnt-signalling-regulates-nuclear-export-of-setdb1-during-skeletal-muscle-terminal-differentiation
#5
Sophie Beyer, Julien Pontis, Elija Schirwis, Valentine Battisti, Anja Rudolf, Fabien Le Grand, Slimane Ait-Si-Ali
The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on the roles of Setdb1 in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation. Ex vivo studies on isolated single myofibres showed that Setdb1 is required for adult muscle stem cells expansion following activation. In vitro studies in skeletal myoblasts confirmed that Setdb1 suppresses terminal differentiation...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27780869/uri-regulates-kap1-phosphorylation-and-transcriptional-repression-via-pp2a-phosphatase-in-prostate-cancer-cells
#6
Paolo Mita, Jeffrey N Savas, Erica M Briggs, Susan Ha, Veena Gnanakkan, John R Yates, Diane M Robins, Gregory David, Jef D Boeke, Michael J Garabedian, Susan K Logan
URI (unconventional prefoldin RPB5 interactor protein) is an unconventional prefoldin, RNA polymerase II interactor that functions as a transcriptional repressor and is part of a larger nuclear protein complex. The components of this complex and the mechanism of transcriptional repression have not been characterized. Here we show that KAP1 (KRAB-associated protein 1) and the protein phosphatase PP2A interact with URI. Mechanistically, we show that KAP1 phosphorylation is decreased following recruitment of PP2A by URI...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27741228/correction-hnrnp-k-coordinates-transcriptional-silencing-by-setdb1-in-embryonic-stem-cells
#7
Peter J Thompson, Vered Dulberg, Kyung-Mee Moon, Leonard J Foster, Carol Chen, Mohammad M Karimi, Matthew C Lorincz
[This corrects the article DOI: 10.1371/journal.pgen.1004933.].
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27732843/atf7ip-mediated-stabilization-of-the-histone-methyltransferase-setdb1-is-essential-for-heterochromatin-formation-by-the-hush-complex
#8
Richard T Timms, Iva A Tchasovnikarova, Robin Antrobus, Gordon Dougan, Paul J Lehner
The histone methyltransferase SETDB1 plays a central role in repressive chromatin processes, but the functional requirement for its binding partner ATF7IP has remained enigmatic. Here, we show that ATF7IP is essential for SETDB1 stability: nuclear SETDB1 protein is degraded by the proteasome upon ablation of ATF7IP. As a result, ATF7IP is critical for repression that requires H3K9 trimethylation by SETDB1, including transgene silencing by the HUSH complex. Furthermore, we show that loss of ATF7IP phenocopies loss of SETDB1 in genome-wide assays...
October 11, 2016: Cell Reports
https://www.readbyqxmd.com/read/27551509/%C3%AE-np63%C3%AE-modulates-histone-methyl-transferase-setdb1-to-transcriptionally-repress-target-genes-in-cancers
#9
C Regina, M Compagnone, A Peschiaroli, A M Lena, G Melino, E Candi
No abstract text is available yet for this article.
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27511731/a-histone-methyltransferase-eset-is-critical-for-t-cell-development
#10
Shoichi Takikita, Ryunosuke Muro, Toshiyuki Takai, Takeshi Otsubo, Yuki I Kawamura, Taeko Dohi, Hiroyo Oda, Masayuki Kitajima, Kenshiro Oshima, Masahira Hattori, Takaho A Endo, Tetsuro Toyoda, John Weis, Yoichi Shinkai, Harumi Suzuki
ESET/SETDB1, one of the major histone methyltransferases, catalyzes histone 3 lysine 9 (H3K9) trimethylation. ESET is critical for suppressing expression of retroviral elements in embryonic stem cells; however, its role in the immune system is not known. We found that thymocyte-specific deletion of ESET caused impaired T cell development, with CD8 lineage cells being most severely affected. Increased apoptosis of CD8 single-positive cells was observed, and TCR-induced ERK activation was severely inhibited in ESET(-/-) thymocytes...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27349785/the-h3k9-methyltransferase-setdb1-regulates-tlr4-mediated-inflammatory-responses-in-macrophages
#11
Rumi Hachiya, Takuya Shiihashi, Ibuki Shirakawa, Yorihiro Iwasaki, Yoshihiro Matsumura, Yumiko Oishi, Yukiteru Nakayama, Yoshihiro Miyamoto, Ichiro Manabe, Kozue Ochi, Miyako Tanaka, Nobuhito Goda, Juro Sakai, Takayoshi Suganami, Yoshihiro Ogawa
Proinflammatory cytokine production in macrophages involves multiple regulatory mechanisms, which are affected by environmental and intrinsic stress. In particular, accumulating evidence has suggested epigenetic control of macrophage differentiation and function mainly in vitro. SET domain, bifurcated 1 (Setdb1, also known as Eset) is a histone 3 lysine 9 (H3K9)-specific methyltransferase and is essential for early development of embryos. Here we demonstrate that Setdb1 in macrophages potently suppresses Toll-like receptor 4 (TLR4)-mediated expression of proinflammatory cytokines including interleukin-6 through its methyltransferase activity...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27334461/setdb1-is-a-new-promising-target-in-hcc-therapy
#12
Carla Cicchini, Cecilia Battistelli, Marco Tripodi
No abstract text is available yet for this article.
June 3, 2016: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/27317807/the-methyltransferase-setdb1-is-essential-for-meiosis-and-mitosis-in-mouse-oocytes-and-early-embryos
#13
Angeline Eymery, Zichuan Liu, Evgeniy A Ozonov, Michael B Stadler, Antoine H F M Peters
Oocytes develop the competence for meiosis and early embryogenesis during their growth. Setdb1 is a histone H3 lysine 9 (H3K9) methyltransferase required for post-implantation development and has been implicated in the transcriptional silencing of genes and endogenous retroviral elements (ERVs). To address its role in oogenesis and pre-implantation development, we conditionally deleted Setdb1 in growing oocytes. Loss of Setdb1 expression greatly impaired meiosis. It delayed meiotic resumption, altered the dynamics of chromatin condensation, and impaired kinetochore-spindle interactions, bipolar spindle organization and chromosome segregation in more mature oocytes...
August 1, 2016: Development
https://www.readbyqxmd.com/read/27317259/the-costimulatory-receptor-ox40-inhibits-interleukin-17-expression-through-activation-of-repressive-chromatin-remodeling-pathways
#14
Xiang Xiao, Xiaomin Shi, Yihui Fan, Chenglin Wu, Xiaolong Zhang, Laurie Minze, Wentao Liu, Rafik M Ghobrial, Peixiang Lan, Xian Chang Li
T helper 17 (Th17) cells are prominently featured in multiple autoimmune diseases, but the regulatory mechanisms that control Th17 cell responses are poorly defined. Here we found that stimulation of OX40 triggered a robust chromatin remodeling response and produced a "closed" chromatin structure at interleukin-17 (IL-17) locus to inhibit Th17 cell function. OX40 activated the NF-κB family member RelB, and RelB recruited the histone methyltransferases G9a and SETDB1 to the Il17 locus to deposit "repressive" chromatin marks at H3K9 sites, and consequently repressing IL-17 expression...
June 21, 2016: Immunity
https://www.readbyqxmd.com/read/27301860/setdb1-maintains-hematopoietic-stem-and-progenitor-cells-by-restricting-the-ectopic-activation-of-nonhematopoietic-genes
#15
Shuhei Koide, Motohiko Oshima, Keiyo Takubo, Satoshi Yamazaki, Eriko Nitta, Atsunori Saraya, Kazumasa Aoyama, Yuko Kato, Satoru Miyagi, Yaeko Nakajima-Takagi, Tetsuhiro Chiba, Hirotaka Matsui, Fumio Arai, Yutaka Suzuki, Hiroshi Kimura, Hiromitsu Nakauchi, Toshio Suda, Yoichi Shinkai, Atsushi Iwama
Setdb1, also known as Eset, is a methyltransferase that catalyzes trimethylation of H3K9 (H3K9me3) and plays an essential role in the silencing of endogenous retroviral elements (ERVs) in the developing embryo and embryonic stem cells (ESCs). Its role in somatic stem cells, however, remains unclear because of the early death of Setdb1-deficient embryos. We demonstrate here that Setdb1 is the first H3K9 methyltransferase shown to be essential for the maintenance of hematopoietic stem and progenitor cells (HSPCs) in mice...
August 4, 2016: Blood
https://www.readbyqxmd.com/read/27237050/e3-independent-constitutive-monoubiquitination-complements-histone-methyltransferase-activity-of-setdb1
#16
Lidong Sun, Jia Fang
Ubiquitination typically occurs through the sequential action of three enzymes catalyzing ubiquitin activation (E1), conjugation (E2), and ligation (E3) and regulates diverse eukaryotic cellular processes. Although monoubiquitination commonly confers nondegradative activities, mechanisms underlying its temporal and spatial regulation and functional plasticity still remain largely unknown. Here we demonstrate that SETDB1, a major histone H3K9 methyltransferase is monoubiquitinated at the evolutionarily conserved lysine-867 in its SET-Insertion domain...
June 16, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27225916/-hepatitis-b-virus-and-chromatin-remodeling-hbx-counteracts-setdb1-hp1-h3k9me3-transcriptional-silencing
#17
Lise Rivière, Laetitia Gérossier, Olivier Hantz, Christine Neuveut
No abstract text is available yet for this article.
May 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27217481/dna-cpg-methylation-5-methylcytosine-and-its-derivative-5-hydroxymethylcytosine-alter-histone-posttranslational-modifications-at-the-pomc-promoter-affecting-the-impact-of-perinatal-diet-on-leanness-and-obesity-of-the-offspring
#18
Asaf Marco, Tatiana Kisliouk, Tzlil Tabachnik, Aron Weller, Noam Meiri
A maternal high-fat diet (HFD) alters the offspring's feeding regulation, leading to obesity. This phenomenon is partially mediated by aberrant expression of the hypothalamic anorexigenic neuropeptide proopiomelanocortin (POMC). Nevertheless, although some individual offspring suffer from morbid obesity, others escape the malprogramming. It is suggested that this difference is due to epigenetic programming. In this study, we report that in lean offspring of non-HFD-fed dams, essential promoter regions for Pomc expression were enriched with 5-hydroxymethylcytosine (5hmC) together with a reduction in the level of 5-methylcytosine (5mC)...
August 2016: Diabetes
https://www.readbyqxmd.com/read/27195021/setdb1-mediated-h3k9-methylation-is-enriched-on-the-inactive-x-and-plays-a-role-in-its-epigenetic-silencing
#19
Andrew Keniry, Linden J Gearing, Natasha Jansz, Joy Liu, Aliaksei Z Holik, Peter F Hickey, Sarah A Kinkel, Darcy L Moore, Kelsey Breslin, Kelan Chen, Ruijie Liu, Catherine Phillips, Miha Pakusch, Christine Biben, Julie M Sheridan, Benjamin T Kile, Catherine Carmichael, Matthew E Ritchie, Douglas J Hilton, Marnie E Blewitt
BACKGROUND: The presence of histone 3 lysine 9 (H3K9) methylation on the mouse inactive X chromosome has been controversial over the last 15 years, and the functional role of H3K9 methylation in X chromosome inactivation in any species has remained largely unexplored. RESULTS: Here we report the first genomic analysis of H3K9 di- and tri-methylation on the inactive X: we find they are enriched at the intergenic, gene poor regions of the inactive X, interspersed between H3K27 tri-methylation domains found in the gene dense regions...
2016: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/27174370/the-enzymes-lsd1-and-set1a-cooperate-with-the-viral-protein-hbx-to-establish-an-active-hepatitis-b-viral-chromatin-state
#20
Valentina Alarcon, Sergio Hernández, Lorena Rubio, Francisca Alvarez, Yvo Flores, Manuel Varas-Godoy, Giancarlo V De Ferrari, Michael Kann, Rodrigo A Villanueva, Alejandra Loyola
With about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1)...
2016: Scientific Reports
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