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https://www.readbyqxmd.com/read/28199849/quantitative-flim-fret-microscopy-to-monitor-nanoscale-chromatin-compaction-in%C3%A2-vivo-reveals-structural-roles-of-condensin-complexes
#1
David Llères, Aymeric P Bailly, Aurélien Perrin, David G Norman, Dimitris P Xirodimas, Robert Feil
How metazoan genomes are structured at the nanoscale in living cells and tissues remains unknown. Here, we adapted a quantitative FRET (Förster resonance energy transfer)-based fluorescence lifetime imaging microscopy (FLIM) approach to assay nanoscale chromatin compaction in living organisms. Caenorhabditis elegans was chosen as a model system. By measuring FRET between histone-tagged fluorescent proteins, we visualized distinct chromosomal regions and quantified the different levels of nanoscale compaction in meiotic cells...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28106510/a-drive-in-suvs-from-development-to-disease
#2
Vinay Kumar Rao, Ananya Pal, Reshma Taneja
Progression of cells through distinct phases of the cell cycle, and transition into out-of-cycling states, such as terminal differentiation and senescence, is accompanied by specific patterns of gene expression. These cell fate decisions are mediated not only by distinct transcription factors, but also chromatin modifiers that establish heritable epigenetic patterns. Lysine methyltransferases (KMTs) that mediate methylation marks on histone and non-histone proteins are now recognized as important regulators of gene expression in cycling and non-cycling cells...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28076698/emerging-role-of-setdb1-as-a-therapeutic-target
#3
Archana Venkataramana Karanth, Radhika Radha Maniswami, Seema Prashanth, Hemalatha Govindaraj, Ramya Padmavathy, Sooriya Kumar Jegatheesan, Ramesh Mullangi, Sriram Rajagopal
Epigenetic changes lead to aberrant gene expression in cancer. SETDB1, a histone lysine methyltransferase plays an important role in methylation and gene silencing. Aberrant histone methylation at H3K9 by SETDB1 promotes silencing of tumor suppressor genes and thus contributes to carcinogenesis. Recent studies indicate that SETDB1 is abnormally expressed in various human cancer conditions which contributed to enhanced tumor growth and metastasis. Hence, SETDB1 appears to be a promising epigenetic target for therapeutic intervention...
January 20, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27890611/histone-methyltransferase-setdb1-is-indispensable-for-meckel-s-cartilage-development
#4
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...
January 22, 2017: 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
#5
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
#6
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
#7
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...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27790377/canonical-wnt-signalling-regulates-nuclear-export-of-setdb1-during-skeletal-muscle-terminal-differentiation
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
Carla Cicchini, Cecilia Battistelli, Marco Tripodi
No abstract text is available yet for this article.
December 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
#16
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
#17
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
#18
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
#19
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
#20
Lise Rivière, Laetitia Gérossier, Olivier Hantz, Christine Neuveut
No abstract text is available yet for this article.
May 2016: Médecine Sciences: M/S
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