Characterization of the NIPBL Protein Associated with Cornelia De Lange Syndrome
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Global Characteristics of Csig-Associated Gene Expression Changes in Human Hek293 Cells and the Implications for Csig Regulating Cell Proliferation and Senescence
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Frontiers - Publisher Connector ORIGINAL RESEARCH published: 15 May 2015 doi: 10.3389/fendo.2015.00069 Global characteristics of CSIG-associated gene expression changes in human HEK293 cells and the implications for CSIG regulating cell proliferation and senescence Liwei Ma, Wenting Zhao, Feng Zhu, Fuwen Yuan, Nan Xie, Tingting Li, Pingzhang Wang and Tanjun Tong* Research Center on Aging. Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Edited by: Beijing, China Wen Zhou, Columbia University, USA Reviewed by: Cellular senescence-inhibited gene (CSIG), also named as ribosomal_L1 domain-contain- Jian Zhong, ing 1 (RSL1D1), is implicated in various processes including cell cycle regulation, cellular Mayo Clinic, USA Xiaoxu Zheng, senescence, apoptosis, and tumor metastasis. However, little is known about the regulatory University of Maryland Baltimore, USA mechanism underlying its functions. To screen important targets and signaling pathways Wensi Tao, University of Miami, USA modulated by CSIG, we compared the gene expression profiles in CSIG-silencing and control *Correspondence: HEK293 cells using Affymetrix microarray Human Genome U133 Plus 2.0 GeneChips. A Tanjun Tong, total of 590 genes displayed statistically significant expression changes, with 279 genes Department of Biochemistry and up-regulated and 311 down-regulated, respectively. These genes are involved in a broad array Molecular Biology, Research Center on Aging, Peking University Health of biological processes, mainly in transcriptional regulation, cell cycle, signal transduction, Science Center, 38 Xueyuan Road, oxidation reduction, development, and cell adhesion. -
JB Review Biochemical and Structural Properties of Heterochromatin Protein 1: Understanding Its Role in Chromatin Assembly
J. Biochem. 2014;1Journal10 doi:10.1093/jb/mvu032 of Biochemistry Advance Access published June 4, 2014 JB Review Biochemical and structural properties of heterochromatin protein 1: understanding its role in chromatin assembly Received March 20, 2014; accepted April 9, 2014; published online May 13, 2014 Gohei Nishibuchi and Jun-ichi Nakayama* homologues and isoforms have been identified in eu- karyotic organisms, ranging from fission yeast to Graduate School of Natural Sciences, Nagoya City University, mammals, flies, and nematodes (69). In mammals, Nagoya 467-8501, Japan the three HP1 isoforms HP1a, HP1b and HP1g *Jun-ichi Nakayama, Graduate School of Natural Sciences, Nagoya (Fig. 1A) have different localization patterns within City University, 1 Yamanohata, Mizuho-cho, Mizuho-ku, Nagoya cells (11, 12). Mice deficient for each HP1 isoform ex- 467-8501, Japan. Tel: þ81-52-872-5838, Fax: þ81-52-872-5866, email: [email protected] hibit different phenotypes (1315), indicating that the isoforms have distinct functions in forming higher- Heterochromatin protein 1 (HP1) is an evolutionarily order chromatin structures. conserved chromosomal protein that binds lysine HP1-family proteins share a basic structure consist- Downloaded from 9-methylated histone H3 (H3K9me), a hallmark of het- ing of an amino-terminal chromodomain (CD) and a erochromatin, and plays a crucial role in forming carboxyl-terminal chromo shadow domain (CSD) higher-order chromatin structures. HP1 has an N-ter- linked by an unstructured hinge region (16). The CD minal chromodomain and a C-terminal chromo shadow functions as a binding module that targets lysine domain, linked by an unstructured hinge region. -
Functional Roles of Bromodomain Proteins in Cancer
cancers Review Functional Roles of Bromodomain Proteins in Cancer Samuel P. Boyson 1,2, Cong Gao 3, Kathleen Quinn 2,3, Joseph Boyd 3, Hana Paculova 3 , Seth Frietze 3,4,* and Karen C. Glass 1,2,4,* 1 Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Colchester, VT 05446, USA; [email protected] 2 Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA; [email protected] 3 Department of Biomedical and Health Sciences, University of Vermont, Burlington, VT 05405, USA; [email protected] (C.G.); [email protected] (J.B.); [email protected] (H.P.) 4 University of Vermont Cancer Center, Burlington, VT 05405, USA * Correspondence: [email protected] (S.F.); [email protected] (K.C.G.) Simple Summary: This review provides an in depth analysis of the role of bromodomain-containing proteins in cancer development. As readers of acetylated lysine on nucleosomal histones, bromod- omain proteins are poised to activate gene expression, and often promote cancer progression. We examined changes in gene expression patterns that are observed in bromodomain-containing proteins and associated with specific cancer types. We also mapped the protein–protein interaction network for the human bromodomain-containing proteins, discuss the cellular roles of these epigenetic regu- lators as part of nine different functional groups, and identify bromodomain-specific mechanisms in cancer development. Lastly, we summarize emerging strategies to target bromodomain proteins in cancer therapy, including those that may be essential for overcoming resistance. Overall, this review provides a timely discussion of the different mechanisms of bromodomain-containing pro- Citation: Boyson, S.P.; Gao, C.; teins in cancer, and an updated assessment of their utility as a therapeutic target for a variety of Quinn, K.; Boyd, J.; Paculova, H.; cancer subtypes. -
Topologically Associating Domain Boundaries Are Commonly
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.06.443037; this version posted May 7, 2021. 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-NC 4.0 International license. Topologically Associating Domain Boundaries are Commonly Required for Normal Genome Function Sudha Rajderkar1, Iros Barozzi1,2,3, Yiwen Zhu1, Rong Hu4, Yanxiao Zhang4, Bin Li4, Yoko Fukuda- Yuzawa1,5, Guy Kelman1,6, Adyam Akeza1, Matthew J. Blow15, Quan Pham1, Anne N. Harrington1, Janeth Godoy1, Eman M. Meky1, Kianna von Maydell1, Catherine S. Novak1, Ingrid Plajzer-Frick1, Veena Afzal1, Stella Tran1, Michael E. Talkowski7,8,9, K. C. Kent Lloyd10,11, Bing Ren4,12,13,14, Diane E. Dickel1,*, Axel Visel1,15,16,*, Len A. Pennacchio1,15, 17,* 1 Environmental Genomics & System Biology Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720, USA. 2 Institute of Cancer Research Medical University of Vienna, Borschkegasse 8a 1090, Vienna, Austria. 3 Department of Surgery and Cancer, Imperial College London, London, UK. 4 Ludwig Institute for Cancer Research, La Jolla, CA, USA. 5 Institute of Advanced Biosciences, Keio University, Tsuruoka, Yamagata, Japan. 6 The Jerusalem Center for Personalized Computational Medicine, Hebrew University of Jerusalem, Jerusalem, Israel. 7 Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. 8 Program in Medical and Population Genetics and Stanley Center for Psychiatric Disorders, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142, USA. -
Supplementary Table S1. Upregulated Genes Differentially
Supplementary Table S1. Upregulated genes differentially expressed in athletes (p < 0.05 and 1.3-fold change) Gene Symbol p Value Fold Change 221051_s_at NMRK2 0.01 2.38 236518_at CCDC183 0.00 2.05 218804_at ANO1 0.00 2.05 234675_x_at 0.01 2.02 207076_s_at ASS1 0.00 1.85 209135_at ASPH 0.02 1.81 228434_at BTNL9 0.03 1.81 229985_at BTNL9 0.01 1.79 215795_at MYH7B 0.01 1.78 217979_at TSPAN13 0.01 1.77 230992_at BTNL9 0.01 1.75 226884_at LRRN1 0.03 1.74 220039_s_at CDKAL1 0.01 1.73 236520_at 0.02 1.72 219895_at TMEM255A 0.04 1.72 201030_x_at LDHB 0.00 1.69 233824_at 0.00 1.69 232257_s_at 0.05 1.67 236359_at SCN4B 0.04 1.64 242868_at 0.00 1.63 1557286_at 0.01 1.63 202780_at OXCT1 0.01 1.63 1556542_a_at 0.04 1.63 209992_at PFKFB2 0.04 1.63 205247_at NOTCH4 0.01 1.62 1554182_at TRIM73///TRIM74 0.00 1.61 232892_at MIR1-1HG 0.02 1.61 204726_at CDH13 0.01 1.6 1561167_at 0.01 1.6 1565821_at 0.01 1.6 210169_at SEC14L5 0.01 1.6 236963_at 0.02 1.6 1552880_at SEC16B 0.02 1.6 235228_at CCDC85A 0.02 1.6 1568623_a_at SLC35E4 0.00 1.59 204844_at ENPEP 0.00 1.59 1552256_a_at SCARB1 0.02 1.59 1557283_a_at ZNF519 0.02 1.59 1557293_at LINC00969 0.03 1.59 231644_at 0.01 1.58 228115_at GAREM1 0.01 1.58 223687_s_at LY6K 0.02 1.58 231779_at IRAK2 0.03 1.58 243332_at LOC105379610 0.04 1.58 232118_at 0.01 1.57 203423_at RBP1 0.02 1.57 AMY1A///AMY1B///AMY1C///AMY2A///AMY2B// 208498_s_at 0.03 1.57 /AMYP1 237154_at LOC101930114 0.00 1.56 1559691_at 0.01 1.56 243481_at RHOJ 0.03 1.56 238834_at MYLK3 0.01 1.55 213438_at NFASC 0.02 1.55 242290_at TACC1 0.04 1.55 ANKRD20A1///ANKRD20A12P///ANKRD20A2/// -
The Mutational Landscape of Myeloid Leukaemia in Down Syndrome
cancers Review The Mutational Landscape of Myeloid Leukaemia in Down Syndrome Carini Picardi Morais de Castro 1, Maria Cadefau 1,2 and Sergi Cuartero 1,2,* 1 Josep Carreras Leukaemia Research Institute (IJC), Campus Can Ruti, 08916 Badalona, Spain; [email protected] (C.P.M.d.C); [email protected] (M.C.) 2 Germans Trias i Pujol Research Institute (IGTP), Campus Can Ruti, 08916 Badalona, Spain * Correspondence: [email protected] Simple Summary: Leukaemia occurs when specific mutations promote aberrant transcriptional and proliferation programs, which drive uncontrolled cell division and inhibit the cell’s capacity to differentiate. In this review, we summarize the most frequent genetic lesions found in myeloid leukaemia of Down syndrome, a rare paediatric leukaemia specific to individuals with trisomy 21. The evolution of this disease follows a well-defined sequence of events and represents a unique model to understand how the ordered acquisition of mutations drives malignancy. Abstract: Children with Down syndrome (DS) are particularly prone to haematopoietic disorders. Paediatric myeloid malignancies in DS occur at an unusually high frequency and generally follow a well-defined stepwise clinical evolution. First, the acquisition of mutations in the GATA1 transcription factor gives rise to a transient myeloproliferative disorder (TMD) in DS newborns. While this condition spontaneously resolves in most cases, some clones can acquire additional mutations, which trigger myeloid leukaemia of Down syndrome (ML-DS). These secondary mutations are predominantly found in chromatin and epigenetic regulators—such as cohesin, CTCF or EZH2—and Citation: de Castro, C.P.M.; Cadefau, in signalling mediators of the JAK/STAT and RAS pathways. -
S41467-020-18249-3.Pdf
ARTICLE https://doi.org/10.1038/s41467-020-18249-3 OPEN Pharmacologically reversible zonation-dependent endothelial cell transcriptomic changes with neurodegenerative disease associations in the aged brain Lei Zhao1,2,17, Zhongqi Li 1,2,17, Joaquim S. L. Vong2,3,17, Xinyi Chen1,2, Hei-Ming Lai1,2,4,5,6, Leo Y. C. Yan1,2, Junzhe Huang1,2, Samuel K. H. Sy1,2,7, Xiaoyu Tian 8, Yu Huang 8, Ho Yin Edwin Chan5,9, Hon-Cheong So6,8, ✉ ✉ Wai-Lung Ng 10, Yamei Tang11, Wei-Jye Lin12,13, Vincent C. T. Mok1,5,6,14,15 &HoKo 1,2,4,5,6,8,14,16 1234567890():,; The molecular signatures of cells in the brain have been revealed in unprecedented detail, yet the ageing-associated genome-wide expression changes that may contribute to neurovas- cular dysfunction in neurodegenerative diseases remain elusive. Here, we report zonation- dependent transcriptomic changes in aged mouse brain endothelial cells (ECs), which pro- minently implicate altered immune/cytokine signaling in ECs of all vascular segments, and functional changes impacting the blood–brain barrier (BBB) and glucose/energy metabolism especially in capillary ECs (capECs). An overrepresentation of Alzheimer disease (AD) GWAS genes is evident among the human orthologs of the differentially expressed genes of aged capECs, while comparative analysis revealed a subset of concordantly downregulated, functionally important genes in human AD brains. Treatment with exenatide, a glucagon-like peptide-1 receptor agonist, strongly reverses aged mouse brain EC transcriptomic changes and BBB leakage, with associated attenuation of microglial priming. We thus revealed tran- scriptomic alterations underlying brain EC ageing that are complex yet pharmacologically reversible. -
Gene Regulation by Cohesin in Cancer: Is the Ring an Unexpected Party to Proliferation?
Published OnlineFirst September 22, 2011; DOI: 10.1158/1541-7786.MCR-11-0382 Molecular Cancer Review Research Gene Regulation by Cohesin in Cancer: Is the Ring an Unexpected Party to Proliferation? Jenny M. Rhodes, Miranda McEwan, and Julia A. Horsfield Abstract Cohesin is a multisubunit protein complex that plays an integral role in sister chromatid cohesion, DNA repair, and meiosis. Of significance, both over- and underexpression of cohesin are associated with cancer. It is generally believed that cohesin dysregulation contributes to cancer by leading to aneuploidy or chromosome instability. For cancers with loss of cohesin function, this idea seems plausible. However, overexpression of cohesin in cancer appears to be more significant for prognosis than its loss. Increased levels of cohesin subunits correlate with poor prognosis and resistance to drug, hormone, and radiation therapies. However, if there is sufficient cohesin for sister chromatid cohesion, overexpression of cohesin subunits should not obligatorily lead to aneuploidy. This raises the possibility that excess cohesin promotes cancer by alternative mechanisms. Over the last decade, it has emerged that cohesin regulates gene transcription. Recent studies have shown that gene regulation by cohesin contributes to stem cell pluripotency and cell differentiation. Of importance, cohesin positively regulates the transcription of genes known to be dysregulated in cancer, such as Runx1, Runx3, and Myc. Furthermore, cohesin binds with estrogen receptor a throughout the genome in breast cancer cells, suggesting that it may be involved in the transcription of estrogen-responsive genes. Here, we will review evidence supporting the idea that the gene regulation func- tion of cohesin represents a previously unrecognized mechanism for the development of cancer. -
The Emerging Role of Cohesin in the DNA Damage Response
G C A T T A C G G C A T genes Review The Emerging Role of Cohesin in the DNA Damage Response Ireneusz Litwin * , Ewa Pilarczyk and Robert Wysocki Institute of Experimental Biology, University of Wroclaw, 50-328 Wroclaw, Poland; [email protected] (E.P.); [email protected] (R.W.) * Correspondence: [email protected]; Tel.: +48-71-375-4126 Received: 29 October 2018; Accepted: 21 November 2018; Published: 28 November 2018 Abstract: Faithful transmission of genetic material is crucial for all organisms since changes in genetic information may result in genomic instability that causes developmental disorders and cancers. Thus, understanding the mechanisms that preserve genome integrity is of fundamental importance. Cohesin is a multiprotein complex whose canonical function is to hold sister chromatids together from S-phase until the onset of anaphase to ensure the equal division of chromosomes. However, recent research points to a crucial function of cohesin in the DNA damage response (DDR). In this review, we summarize recent advances in the understanding of cohesin function in DNA damage signaling and repair. First, we focus on cohesin architecture and molecular mechanisms that govern sister chromatid cohesion. Next, we briefly characterize the main DDR pathways. Finally, we describe mechanisms that determine cohesin accumulation at DNA damage sites and discuss possible roles of cohesin in DDR. Keywords: cohesin; cohesin loader; DNA double-strand breaks; replication stress; DNA damage tolerance 1. Introduction Genomes of all living organisms are continuously challenged by endogenous and exogenous insults that threaten genome stability. It has been estimated that human cells suffer more than 70,000 DNA lesions per day, most of which are single-strand DNA breaks (SSBs) [1]. -
The Arabidopsis LHP1 Protein Is a Component of Euchromatin
Planta (2005) 222: 910–925 DOI 10.1007/s00425-005-0129-4 ORIGINAL ARTICLE Marc Libault Æ Federico Tessadori Æ Sophie Germann Berend Snijder Æ Paul Fransz Æ Vale´rie Gaudin The Arabidopsis LHP1 protein is a component of euchromatin Received: 11 June 2005 / Accepted: 29 August 2005 / Published online: 22 October 2005 Ó Springer-Verlag 2005 Abstract The HP1 family proteins are involved in several A. thaliana HP1 homolog with the mammal HP1c iso- aspects of chromatin function and regulation in Dro- form, besides specific plant properties. sophila, mammals and the fission yeast. Here we inves- tigate the localization of LHP1, the unique Arabidopsis Keywords Arabidopsis Æ Chromatin Æ Heterochromatin thaliana HP1 homolog known at present time, to ap- protein 1 Æ Mitosis Æ Nucleolus proach its function. A functional LHP1–GFP fusion protein, able to restore the wild-type phenotype in the Abbreviations PI: Propidium iodide Æ DAPI: lhp1 mutant, was used to analyze the subnuclear distri- 4¢,6-diamidino-2-phenylindole Æ HP1: Heterochromatin bution of LHP1 in both A. thaliana and Nicotiana protein 1 Æ CD: Chromo domain Æ CSD: Chromo tabacum.InA. thaliana interphase nuclei, LHP1 was shadow domain Æ HR: Hinge region Æ RHF: Relative predominantly located outside the heterochromatic heterochromatin fraction Æ FISH: Fluorescent in-situ chromocenters. No major aberrations were observed in hybridization Æ NLS: Nuclear localization heterochromatin content or chromocenter organization signal Æ NoLS: Nucleolar localization signal in lhp1 plants. These data indicate that LHP1 is mainly involved in euchromatin organization in A. thaliana.In tobacco BY-2 cells, the LHP1 distribution, although in foci, slightly differed suggesting that LHP1 localization Introduction is determined by the underlying genome organization of plant species. -
Intact Nucleosomal Context Enables Chromodomain Reader
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.070136; this version posted April 30, 2020. 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. Intact nucleosomal context enables chromodomain reader MRG15 to distinguish H3K36me3 from -me2 Sarah Faulkner1,2, Antony M. Couturier2, Brian Josephson1, Tom Watts1, Benjamin G. Davis1,3# and Fumiko Esashi2# 1 Department of Chemistry, University of Oxford, 12 Mansfield Rd, Oxford OX1 3TA, United Kingdom 2 Sir William Dunn School of Pathology, University of Oxford, S Parks Rd, Oxford OX1 3RE, United Kingdom 3 The Rosalind Franklin Institute, Oxfordshire, OX11 0FA, United Kingdom #To whom correspondence should be addressed: [email protected] and [email protected] Keywords: chromodomain, H3K36 methylation, MRG15, nucleosome, SETD2 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.30.070136; this version posted April 30, 2020. 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. Abstract A wealth of in vivo evidence demonstrates the physiological importance of histone H3 trimethylation at lysine 36 (H3K36me3), to which chromodomain-containing proteins, such as MRG15, bind preferentially compared to their dimethyl (H3K36me2) counterparts. However, in vitro studies using isolated H3 peptides have failed to recapitulate a causal interaction. Here, we show that MRG15 can clearly discriminate between synthetic, fully intact model nucleosomes containing H3K36me2 and H3K36me3. MRG15 docking studies, along with experimental observations and nucleosome structure analysis suggest a model where the H3K36 side chain is sequestered in intact nucleosomes via a hydrogen bonding interaction with the DNA backbone, which is abrogated when the third methyl group is added to form H3K36me3. -
Chromatin Condensation and Recruitment of PHD Finger Proteins
6102–6112 Nucleic Acids Research, 2016, Vol. 44, No. 13 Published online 25 March 2016 doi: 10.1093/nar/gkw193 Chromatin condensation and recruitment of PHD finger proteins to histone H3K4me3 are mutually exclusive Jovylyn Gatchalian1,†, Carmen Mora Gallardo2,†, Stephen A. Shinsky3, Ruben Rosas Ospina1, Andrea Mansilla Liendo2, Krzysztof Krajewski3, Brianna J. Klein1, Forest H. Andrews1, Brian D. Strahl3, Karel H. M. van Wely2,* and Tatiana G. Kutateladze1,* 1Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA, 2Department of Immunology and Oncology, Centro Nacional de Biotecnolog´ıa/CSIC, 28049 Madrid, Spain and 3Department of Biochemistry & Biophysics, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA Received January 06, 2016; Revised March 12, 2016; Accepted March 15, 2016 ABSTRACT modifications (PTMs), including acetylation and methyla- tion of lysine, methylation of arginine, and phosphorylation Histone post-translational modifications, and spe- of serine and threonine. Over 500 histone PTMs have been cific combinations they create, mediate a wide range identified by mass spectrometry analysis, and a number of of nuclear events. However, the mechanistic bases these modifications, or epigenetic marks, have been shown for recognition of these combinations have not been to modulate chromatin structure and cell cycle specific pro- elucidated. Here, we characterize crosstalk between cesses (1). H3T3 and H3T6 phosphorylation, occurring in mito- Methylation of histone H3 at lysine 4 is one of the canon- sis, and H3K4me3, a mark associated with active ical PTMs (2–4). The trimethylated species (H3K4me3), transcription. We detail the molecular mechanisms which is found primarily in active promoters, is impli- by which H3T3ph/K4me3/T6ph switches mediate ac- cated in transcriptional regulation (5).