Structure of the Tripartite Motif of KAP1/TRIM28 Identifies Molecular Interfaces Required for Transcriptional Silencing of Retrotransposons
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model
Downloaded from http://www.jimmunol.org/ by guest on September 25, 2021 T + is online at: average * The Journal of Immunology , 34 of which you can access for free at: 2016; 197:1477-1488; Prepublished online 1 July from submission to initial decision 4 weeks from acceptance to publication 2016; doi: 10.4049/jimmunol.1600589 http://www.jimmunol.org/content/197/4/1477 Molecular Profile of Tumor-Specific CD8 Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. Waugh, Sonia M. Leach, Brandon L. Moore, Tullia C. Bruno, Jonathan D. Buhrman and Jill E. Slansky J Immunol cites 95 articles Submit online. Every submission reviewed by practicing scientists ? is published twice each month by Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts http://jimmunol.org/subscription Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html http://www.jimmunol.org/content/suppl/2016/07/01/jimmunol.160058 9.DCSupplemental This article http://www.jimmunol.org/content/197/4/1477.full#ref-list-1 Information about subscribing to The JI No Triage! Fast Publication! Rapid Reviews! 30 days* Why • • • Material References Permissions Email Alerts Subscription Supplementary The Journal of Immunology The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. This information is current as of September 25, 2021. The Journal of Immunology Molecular Profile of Tumor-Specific CD8+ T Cell Hypofunction in a Transplantable Murine Cancer Model Katherine A. -
Brd4 Bridges the Transcriptional Regulators, Aire and P-Tefb, to Promote Elongation of Peripheral-Tissue Antigen Transcripts In
Brd4 bridges the transcriptional regulators, Aire and PNAS PLUS P-TEFb, to promote elongation of peripheral-tissue antigen transcripts in thymic stromal cells Hideyuki Yoshidaa, Kushagra Bansala, Uwe Schaeferb, Trevor Chapmanc, Inmaculada Riojac, Irina Proektd, Mark S. Andersone, Rab K. Prinjhac, Alexander Tarakhovskyb, Christophe Benoista,f,1, and Diane Mathisa,f,1 aDivision of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; bLaboratory of Immune Cell Epigenetics and Signaling, The Rockefeller University, New York, NY 10065; cEpinova Discovery Performance Unit, Immuno-Inflammation Therapy Area, Medicines Research Centre, GlaxoSmithKline, Stevenage SG1 2NY, United Kingdom; dDepartment of Microbiology and Immunology, University of California, San Francisco, CA 94143; eDiabetes Center, University of California, San Francisco, CA 94143; and fEvergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115 Contributed by Diane Mathis, June 22, 2015 (sent for review April 20, 2015; reviewed by Leslie J. Berg and Tadatsugu Taniguchi) Aire controls immunologic tolerance by inducing a battery of turning transcription up or down. Indeed, recent data derived thymic transcripts encoding proteins characteristic of peripheral from a variety of experimental approaches argue that Aire’smajor tissues. Its unusually broad effect is achieved by releasing RNA modus operandi is to release promoter-proximal RNA polymerase II polymerase II paused just downstream of transcriptional start (Pol-II) pausing (11–13). sites. We explored Aire’s collaboration with the bromodomain- It has become increasingly clear that the regulation of Pol-II containing protein, Brd4, uncovering an astonishing correspon- pausing is a major nexus of transcriptional control (14), and the dencebetweenthosegenesinducedbyAireandthoseinhibited focus of transcription factors as diverse as NF-κB (15), c-Myc (16), by a small-molecule bromodomain blocker. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
TRIM28 Is Required by the Mouse KRAB Domain Protein ZFP568 to Control Convergent Extension and Morphogenesis of Extra-Embryonic Tissues Maho Shibata1, Kristin E
RESEARCH ARTICLE 5333 Development 138, 5333-5343 (2011) doi:10.1242/dev.072546 © 2011. Published by The Company of Biologists Ltd TRIM28 is required by the mouse KRAB domain protein ZFP568 to control convergent extension and morphogenesis of extra-embryonic tissues Maho Shibata1, Kristin E. Blauvelt1, Karel F. Liem, Jr2 and María J. García-García1,* SUMMARY TRIM28 is a transcriptional regulator that is essential for embryonic development and is implicated in a variety of human diseases. The roles of TRIM28 in distinct biological processes are thought to depend on its interaction with factors that determine its DNA target specificity. However, functional evidence linking TRIM28 to specific co-factors is scarce. chatwo, a hypomorphic allele of Trim28, causes embryonic lethality and defects in convergent extension and morphogenesis of extra-embryonic tissues. These phenotypes are remarkably similar to those of mutants in the Krüppel-associated box (KRAB) zinc finger protein ZFP568, providing strong genetic evidence that ZFP568 and TRIM28 control morphogenesis through a common molecular mechanism. We determined that chatwo mutations decrease TRIM28 protein stability and repressive activity, disrupting both ZFP568-dependent and ZFP568-independent roles of TRIM28. These results, together with the analysis of embryos bearing a conditional inactivation of Trim28 in embryonic-derived tissues, revealed that TRIM28 is differentially required by ZFP568 and other factors during the early stages of mouse embryogenesis. In addition to uncovering novel roles of TRIM28 in convergent extension and morphogenesis of extra-embryonic tissues, our characterization of chatwo mutants demonstrates that KRAB domain proteins are essential to determine some of the biological functions of TRIM28. -
The Structure-Function Relationship of Angular Estrogens and Estrogen Receptor Alpha to Initiate Estrogen-Induced Apoptosis in Breast Cancer Cells S
Supplemental material to this article can be found at: http://molpharm.aspetjournals.org/content/suppl/2020/05/03/mol.120.119776.DC1 1521-0111/98/1/24–37$35.00 https://doi.org/10.1124/mol.120.119776 MOLECULAR PHARMACOLOGY Mol Pharmacol 98:24–37, July 2020 Copyright ª 2020 The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license. The Structure-Function Relationship of Angular Estrogens and Estrogen Receptor Alpha to Initiate Estrogen-Induced Apoptosis in Breast Cancer Cells s Philipp Y. Maximov, Balkees Abderrahman, Yousef M. Hawsawi, Yue Chen, Charles E. Foulds, Antrix Jain, Anna Malovannaya, Ping Fan, Ramona F. Curpan, Ross Han, Sean W. Fanning, Bradley M. Broom, Daniela M. Quintana Rincon, Jeffery A. Greenland, Geoffrey L. Greene, and V. Craig Jordan Downloaded from Departments of Breast Medical Oncology (P.Y.M., B.A., P.F., D.M.Q.R., J.A.G., V.C.J.) and Computational Biology and Bioinformatics (B.M.B.), University of Texas, MD Anderson Cancer Center, Houston, Texas; King Faisal Specialist Hospital and Research (Gen.Org.), Research Center, Jeddah, Kingdom of Saudi Arabia (Y.M.H.); The Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois (R.H., S.W.F., G.L.G.); Center for Precision Environmental Health and Department of Molecular and Cellular Biology (C.E.F.), Mass Spectrometry Proteomics Core (A.J., A.M.), Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Mass Spectrometry Proteomics Core (A.M.), and Dan L. Duncan molpharm.aspetjournals.org -
Epidermal Wnt Signalling Regulates Transcriptome Heterogeneity and Proliferative Fate in Neighbouring Cells
bioRxiv preprint doi: https://doi.org/10.1101/152637; this version posted June 20, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title: Epidermal Wnt signalling regulates transcriptome heterogeneity and proliferative fate in neighbouring cells Arsham Ghahramani1,2 , Giacomo Donati2,3 , Nicholas M. Luscombe1,4,5,† and Fiona M. Watt2,† 1The Francis Crick Institute, 1 Midland Road, London NW1 1AT, United Kingdom 2King’s College London, Centre for Stem Cells and Regenerative Medicine, 28th 8 Floor, Tower Wing, Guy’s Hospital, Great Maze Pond, London SE1 9RT, United Kingdom 3Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Torino, Italy 4UCL Genetics Institute, University College London, London WC1E 6BT, United Kingdom 5Okinawa Institute of Science & Technology Graduate University, Okinawa 904-0495, Japan † Correspondence to: [email protected] and [email protected] Abstract: Canonical Wnt/beta-catenin signalling regulates self-renewal and lineage selection within the mouse epidermis. Although the transcriptional response of keratinocytes that receive a Wnt signal is well characterised, little is known about the mechanism by which keratinocytes in proximity to the Wnt- receiving cell are co-opted to undergo a change in cell fate. To address this, we performed single-cell mRNA-Seq on mouse keratinocytes co-cultured with and without the presence of beta-catenin activated neighbouring cells. We identified seven distinct cell states in cultures that had not been exposed to the beta-catenin stimulus and show that the stimulus redistributes wild type subpopulation proportions. -
RIPK3 Activation Induces TRIM28 Derepression in Cancer Cells And
Park et al. Molecular Cancer (2021) 20:107 https://doi.org/10.1186/s12943-021-01399-3 RESEARCH Open Access RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment Han-Hee Park1,2, Hwa-Ryeon Kim3, Sang-Yeong Park1,2, Sung-Min Hwang1, Sun Mi Hong1, Sangwook Park2,4, Ho Chul Kang2,4, Michael J. Morgan5, Jong-Ho Cha6,7, Dakeun Lee8, Jae-Seok Roe3* and You-Sun Kim1,2* Abstract Background: Necroptosis is emerging as a new target for cancer immunotherapy as it is now recognized as a form of cell death that increases tumor immunogenicity, which would be especially helpful in treating immune-desert tumors. De novo synthesis of inflammatory proteins during necroptosis appears especially important in facilitating increased anti-tumor immune responses. While late-stage transcription mediated by NF-κB during cell death is believed to play a role in this process, it is otherwise unclear what cell signaling events initiate this transactivation of inflammatory genes. Methods: We employed tandem-affinity purification linked to mass spectrometry (TAP-MS), in combination with the analysis of RNA-sequencing (RNA-Seq) datasets to identify the Tripartite Motif Protein 28 (TRIM28) as a candidate co-repressor. Comprehensive biochemical and molecular biology techniques were used to characterize the role of TRIM28 in RIPK3 activation-induced transcriptional and immunomodulatory events. The cell composition estimation module was used to evaluate the correlation between RIPK3/TRIM28 levels and CD8+ T cells or dendritic cells (DC) in all TCGA tumors. Results: We identified TRIM28 as a co-repressor that regulates transcriptional activity during necroptosis. -
Arsenic Hexoxide Has Differential Effects on Cell Proliferation And
www.nature.com/scientificreports OPEN Arsenic hexoxide has diferential efects on cell proliferation and genome‑wide gene expression in human primary mammary epithelial and MCF7 cells Donguk Kim1,7, Na Yeon Park2,7, Keunsoo Kang3, Stuart K. Calderwood4, Dong‑Hyung Cho2, Ill Ju Bae5* & Heeyoun Bunch1,6* Arsenic is reportedly a biphasic inorganic compound for its toxicity and anticancer efects in humans. Recent studies have shown that certain arsenic compounds including arsenic hexoxide (AS4O6; hereafter, AS6) induce programmed cell death and cell cycle arrest in human cancer cells and murine cancer models. However, the mechanisms by which AS6 suppresses cancer cells are incompletely understood. In this study, we report the mechanisms of AS6 through transcriptome analyses. In particular, the cytotoxicity and global gene expression regulation by AS6 were compared in human normal and cancer breast epithelial cells. Using RNA‑sequencing and bioinformatics analyses, diferentially expressed genes in signifcantly afected biological pathways in these cell types were validated by real‑time quantitative polymerase chain reaction and immunoblotting assays. Our data show markedly diferential efects of AS6 on cytotoxicity and gene expression in human mammary epithelial normal cells (HUMEC) and Michigan Cancer Foundation 7 (MCF7), a human mammary epithelial cancer cell line. AS6 selectively arrests cell growth and induces cell death in MCF7 cells without afecting the growth of HUMEC in a dose‑dependent manner. AS6 alters the transcription of a large number of genes in MCF7 cells, but much fewer genes in HUMEC. Importantly, we found that the cell proliferation, cell cycle, and DNA repair pathways are signifcantly suppressed whereas cellular stress response and apoptotic pathways increase in AS6‑treated MCF7 cells. -
A KAP1 Phosphorylation Switch Controls Myod Function During Skeletal Muscle Differentiation
Downloaded from genesdev.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press A KAP1 phosphorylation switch controls MyoD function during skeletal muscle differentiation Kulwant Singh,1,5 Marco Cassano,2,5 Evarist Planet,2 Soji Sebastian,1 Suk Min Jang,2 Gurjeev Sohi,1 Herve Faralli,1 Jinmi Choi,3 Hong-Duk Youn,3 F. Jeffrey Dilworth,1,4 and Didier Trono2 1Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada; 2School of Life Sciences, Ecole Polytechnique Fed erale de Lausanne (EPFL), 1015 Lausanne, Switzerland; 3Department of Biomedical Sciences and Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea; 4Department of Cellular and Molecular Medicine, University of Ottawa, Ontario K1H 8L6, Canada The transcriptional activator MyoD serves as a master controller of myogenesis. Often in partnership with Mef2 (myocyte enhancer factor 2), MyoD binds to the promoters of hundreds of muscle genes in proliferating myoblasts yet activates these targets only upon receiving cues that launch differentiation. What regulates this off/on switch of MyoD function has been incompletely understood, although it is known to reflect the action of chromatin modifiers. Here, we identify KAP1 (KRAB [Kruppel-like€ associated box]-associated protein 1)/TRIM28 (tripartite motif protein 28) as a key regulator of MyoD function. In myoblasts, KAP1 is present with MyoD and Mef2 at many muscle genes, where it acts as a scaffold to recruit not only coactivators such as p300 and LSD1 but also corepressors such as G9a and HDAC1 (histone deacetylase 1), with promoter silencing as the net outcome. -
VHL Inactivation Without Hypoxia Is Sufficient to Achieve Genome Hypermethylation
bioRxiv preprint doi: https://doi.org/10.1101/093310; this version posted December 12, 2016. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. VHL inactivation without hypoxia is sufficient to achieve genome hypermethylation Artem V. Artemov1*, Nadezhda Zhigalova1, Svetlana Zhenilo1, Alexander M. Mazur1 and Egor B. Prokhortchouk1 1 Institute of Bioengineering, Research Center of Biotechnology RAS, Moscow, Russian Federation * [email protected] Abstract VHL inactivation is a key oncogenic event for renal carcinomas. In normoxia, VHL suppresses HIF1a-mediated response to hypoxia. It has previously been shown that hypoxic conditions inhibit TET-dependent hydroxymethylation of cytosines and cause DNA hypermethylation at gene promoters. In this work, we performed VHL inactivation by CRISPR/Cas9 and studied its effects on gene expression and DNA methylation. We showed that even without hypoxia, VHL inactivation leads to hypermethylation of the genome which mainly occurred in AP-1 and TRIM28 binding sites. We also observed promoter hypermethylation of several transcription regulators associated with decreased gene expression. Keywords DNA methylation; VHL; hypoxia; HIF1a; JUN; FOS Introduction Sequencing of cancer genomes was initially aimed to find cancer drivers, or genes, that, once mutated, give a selective advantage to a cancer cell, such as increased proliferation, suppression of apoptosis or the ability to avoid immune response. VHL is a key oncosuppressor gene for kidney cancer. Inactivation of the VHL gene is the most common event in renal carcinomas, accounting for 50{70% of sporadic cases (Scelo et al. 2014; Cancer Genome Atlas Research Network 2013; Thomas et al. -
Hippocampal Dysfunction in the Euchromatin Histone Methyltransferase 1 Heterozygous Knockout Mouse Model for Kleefstra Syndrome
Human Molecular Genetics, 2013, Vol. 22, No. 5 852–866 doi:10.1093/hmg/dds490 Advance Access published on November 21, 2012 Hippocampal dysfunction in the Euchromatin histone methyltransferase 1 heterozygous knockout mouse model for Kleefstra syndrome Monique C.M. Balemans1,2, Nael Nadif Kasri3, Maksym V. Kopanitsa5, Nurudeen O. Afinowi5, Ger Ramakers6, Theo A. Peters4, Andy J. Beynon4, Sanne M. Janssen1, Rik C.J. van Summeren1,2, Jorine M. Eeftens1, Nathalie Eikelenboom1, Marco Benevento3, Makoto Tachibana7, Yoichi Shinkai7, Tjitske Kleefstra1, Hans van Bokhoven1,3,∗,{ and Catharina E.E.M. Van der Zee2,∗,{ 1Department of Human Genetics, 2Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, 3Department of Cognitive Neurosciences, and 4Department of Otorhinolaryngology, Donders Institute for Brain, Downloaded from Cognition and Behavior, Radboud University, Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands 5Synome Ltd, Moneta Building, Babraham Research Campus, Cambridge CB22 3AT, UK, 6Department of Developmental Psychology, University of Amsterdam, Roetersstraat 15, 1018 WB Amsterdam, the Netherlands and 7Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto, University, 53 Shogoin, http://hmg.oxfordjournals.org/ Kawara-cho, Sakyo-ku, Kyoto, Japan Received October 21, 2012; Revised October 21, 2012; Accepted November 15, 2012 Euchromatin histone methyltransferase 1 (EHMT1) is a highly conserved protein that catalyzes mono- and dimethylation of histone H3 lysine 9, thereby epigenetically regulating transcription. Kleefstra syndrome (KS), is caused by haploinsufficiency of the EHMT1 gene, and is an example of an emerging group of intel- lectual disability (ID) disorders caused by genes encoding epigenetic regulators of neuronal gene activity. by guest on March 24, 2016 Little is known about the mechanisms underlying this disorder, prompting us to study the Euchromatin his- tone methyltransferase 1 heterozygous knockout (Ehmt11/2) mice as a model for KS. -
The Histone Methyltransferase SETDB1 Represses Endogenous and Exogenous Retroviruses in B Lymphocytes
The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes Patrick L. Collinsa, Katherine E. Kylea, Takeshi Egawaa, Yoichi Shinkaib, and Eugene M. Oltza,1 aDepartment of Pathology, Washington University School of Medicine, St. Louis, MO 63110; and bCellular Memory Laboratory, RIKEN, Saitama 351-0198, Japan Edited by John V. Moran, University of Michigan, Ann Arbor, MI, and accepted by the Editorial Board May 21, 2015 (received for review November 19, 2014) Genome stability relies on epigenetic mechanisms that enforce tumor viruses (MMTVs). Reintegration of these expressed viruses repression of endogenous retroviruses (ERVs). Current evidence can generate mutations with potential oncogenic consequences suggests that distinct chromatin-based mechanisms repress ERVs (7). Thus, suppression of ERVs via epigenetic mechanisms is es- in cells of embryonic origin (histone methylation dominant) vs. pecially important in adult tissues that harbor cells with a high more differentiated cells (DNA methylation dominant). However, proliferative capacity. the latter aspect of this model has not been tested. Remarkably, Recent studies suggest that the mechanisms of ERV re- and in contrast to the prevailing model, we find that repressive pression in differentiated adult tissues are distinct from those histone methylation catalyzed by the enzyme SETDB1 is critical for in embryonic stem cells (ESCs) or early lineage progenitors (3). In fully differentiated cells, such as fibroblasts, DNA methylation suppression of specific ERV families and exogenous retroviruses in appears to be particularly important for ERV suppression, committed B-lineage cells from adult mice. The profile of ERV whereas HMTs responsible for H3K9me3 are largely dispens- activation in SETDB1-deficient B cells is distinct from that observed able (3, 4).