Mice Lacking Methyl-Cpg Binding Protein 1 Have Deficits in Adult Neurogenesis and Hippocampal Function
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Extreme HOT Regions Are Cpg-Dense Promoters in C. Elegans and Humans
Research Extreme HOT regions are CpG-dense promoters in C. elegans and humans Ron A.-J. Chen, Przemyslaw Stempor, Thomas A. Down, Eva Zeiser, Sky K. Feuer, and Julie Ahringer1 The Gurdon Institute and Department of Genetics, University of Cambridge, Cambridge CB3 0DH, United Kingdom Most vertebrate promoters lie in unmethylated CpG-dense islands, whereas methylation of the more sparsely distributed CpGs in the remainder of the genome is thought to contribute to transcriptional repression. Nonmethylated CG di- nucleotides are recognized by CXXC finger protein 1 (CXXC1, also known as CFP1), which recruits SETD1A (also known as Set1) methyltransferase for trimethylation of histone H3 lysine 4, an active promoter mark. Genomic regions enriched for CpGs are thought to be either absent or irrelevant in invertebrates that lack DNA methylation, such as C. elegans; however, a CXXC1 ortholog (CFP-1) is present. Here we demonstrate that C. elegans CFP-1 targets promoters with high CpG density, and these promoters are marked by high levels of H3K4me3. Furthermore, as for mammalian promoters, high CpG content is associated with nucleosome depletion irrespective of transcriptional activity. We further show that highly occupied target (HOT) regions identified by the binding of a large number of transcription factors are CpG-rich pro- moters in C. elegans and human genomes, suggesting that the unusually high factor association at HOT regions may be a consequence of CpG-linked chromatin accessibility. Our results indicate that nonmethylated CpG-dense sequence is a conserved genomic signal that promotes an open chromatin state, targeting by a CXXC1 ortholog, and H3K4me3 modification in both C. -
Maintenance of Self-Renewal Ability of Mouse Embryonic Stem Cells in The
MaintenanceBlackwellMalden,GTCGenes1365-2443©?117OriginalDnmt1/3a/3bA 2006 TsumuraBlackwell to USA ArticleCells Publishing et Publishing al. triple knockoutInc Ltd ES cells of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b Akiko Tsumura1,4, Tomohiro Hayakawa2, Yuichi Kumaki3,6, Shin-ichiro Takebayashi1, Morito Sakaue1, Chisa Matsuoka1, Kunitada Shimotohno4, Fuyuki Ishikawa5, En Li7, Hiroki R. Ueda3, Jun-ichi Nakayama2 and Masaki Okano1,* 1Laboratory for Mammalian Epigenetic Studies, 2Laboratory for Chromatin Dynamics, and 3Laboratory for Systems Biology, Center for Developmental Biology, RIKEN, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan 4Department of Viral Oncology, Institute for Virus Research, Kyoto University, 53 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8501, Japan 5Department of Gene Mechanisms, Graduate School of Biostudies, Kyoto University, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan 6INTEC Web and Genome Informatics Corp., 1-3-3 Shinsuna, Koto-ku, Tokyo 136-8637, Japan 7Epigenetics Program, Novartis Institute for Biomedical Research, 250 Massachusetts Ave., Cambridge, MA 02139, USA DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b cooperatively regulate cytosine methylation in CpG dinucleotides in mammalian genomes, providing an epigenetic basis for gene silencing and maintenance of genome integrity. Proper CpG methylation is required for the normal growth of various somatic cell types, indicating its essential role in the basic cellular function of mammalian cells. Previous studies using Dnmt1–/– or Dnmt3a–/–Dnmt3b–/– ES cells, however, have shown that undifferentiated embryonic stem (ES) cells can tolerate hypomethylation for their proliferation. In an attempt to investigate the effects of the complete loss of CpG DNA methyltransferase function, we established mouse ES cells lacking all three of these enzymes by gene targeting. -
The Structural Basis for Selective Binding of Non-Methylated Cpg Islands by the CFP1 CXXC Domain
ARTICLE Received 13 Dec 2010 | Accepted 9 Feb 2011 | Published 8 Mar 2011 DOI: 10.1038/ncomms1237 The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain Chao Xu1,*, Chuanbing Bian1,*, Robert Lam1, Aiping Dong1 & Jinrong Min1,2 CFP1 is a CXXC domain-containing protein and an essential component of the SETD1 histone H3K4 methyltransferase complex. CXXC domain proteins direct different chromatin-modifying activities to various chromatin regions. Here, we report crystal structures of the CFP1 CXXC domain in complex with six different CpG DNA sequences. The crescent-shaped CFP1 CXXC domain is wedged into the major groove of the CpG DNA, distorting the B-form DNA, and interacts extensively with the major groove of the DNA. The structures elucidate the molecular mechanism of the non-methylated CpG-binding specificity of the CFP1 CXXC domain. The CpG motif is confined by a tripeptide located in a rigid loop, which only allows the accommodation of the non-methylated CpG dinucleotide. Furthermore, we demonstrate that CFP1 has a preference for a guanosine nucleotide following the CpG motif. 1 Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada. 2 Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. *These authors contributed equally to this work. Correspondence and requests for materials should be addressed to J.M. (email: [email protected]). NATURE COMMUNICATIONS | 2:227 | DOI: 10.1038/ncomms1237 | www.nature.com/naturecommunications © 2011 Macmillan Publishers Limited. All rights reserved. ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/ncomms1237 pG islands contain a high density of CpG content and embrace the promoters of most genes in vertebrate genomes1. -
The Epigenetic Regulator Cfp1
Article in press - uncorrected proof BioMol Concepts, Vol. 1 (2010), pp. 325–334 • Copyright ᮊ by Walter de Gruyter • Berlin • New York. DOI 10.1515/BMC.2010.031 Review The epigenetic regulator Cfp1 David G. Skalnik concept is illustrated by a variety of phenomena, including Wells Center for Pediatric Research, Section of Pediatric X-chromosome inactivation, in which one X chromosome in Hematology/Oncology, Departments of Pediatrics and each cell of a developing female blastocyst becomes irre- Biochemistry and Molecular Biology, Indiana University versibly inactivated; genomic imprinting, in which mater- School of Medicine, 1044 W. Walnut St., Indianapolis, nally and paternally derived alleles of a gene are IN 46202, USA differentially expressed; and the observation that diverse tis- sues express distinct sets of genes to permit unique func- e-mail: [email protected] tional properties, yet each (with rare exceptions) carries identical genetic information (1–4). Epigenetic information is largely encoded within chro- matin structure. A major class of epigenetic modifications is Abstract post-translational modification of histones. Dozens of dis- Numerous epigenetic modifications have been identified and tinct covalent modifications at specific amino acid residues correlated with transcriptionally active euchromatin or have been identified, including acetylation, methylation, repressed heterochromatin and many enzymes responsible phosphorylation, and sumoylation (2, 5, 6). Many of these for the addition and removal of these marks have been char- modifications are tightly correlated with either transcription- acterized. However, less is known regarding how these ally active euchromatin or transcriptionally silenced hetero- enzymes are regulated and targeted to appropriate genomic chromatin. Relatively subtle changes of covalent modifica- locations. -
Noelia Díaz Blanco
Effects of environmental factors on the gonadal transcriptome of European sea bass (Dicentrarchus labrax), juvenile growth and sex ratios Noelia Díaz Blanco Ph.D. thesis 2014 Submitted in partial fulfillment of the requirements for the Ph.D. degree from the Universitat Pompeu Fabra (UPF). This work has been carried out at the Group of Biology of Reproduction (GBR), at the Department of Renewable Marine Resources of the Institute of Marine Sciences (ICM-CSIC). Thesis supervisor: Dr. Francesc Piferrer Professor d’Investigació Institut de Ciències del Mar (ICM-CSIC) i ii A mis padres A Xavi iii iv Acknowledgements This thesis has been made possible by the support of many people who in one way or another, many times unknowingly, gave me the strength to overcome this "long and winding road". First of all, I would like to thank my supervisor, Dr. Francesc Piferrer, for his patience, guidance and wise advice throughout all this Ph.D. experience. But above all, for the trust he placed on me almost seven years ago when he offered me the opportunity to be part of his team. Thanks also for teaching me how to question always everything, for sharing with me your enthusiasm for science and for giving me the opportunity of learning from you by participating in many projects, collaborations and scientific meetings. I am also thankful to my colleagues (former and present Group of Biology of Reproduction members) for your support and encouragement throughout this journey. To the “exGBRs”, thanks for helping me with my first steps into this world. Working as an undergrad with you Dr. -
Thomson, Ross (2011) Solution Structure of Hmbd1 CXXC1. Phd Thesis
Thomson, Ross (2011) Solution structure of hMBD1 CXXC1. PhD thesis http://theses.gla.ac.uk/2714/ Copyright and moral rights for this thesis are retained by the author A copy can be downloaded for personal non-commercial research or study, without prior permission or charge This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given. Glasgow Theses Service http://theses.gla.ac.uk/ [email protected] Solution Structure of hMBD1 CXXC1 A thesis submitted to the COLLEGE OF MEDICAL, VETERINARY & LIFE SCIENCES For the Degree of DOCTOR OF PHILOSOPHY By Ross Thomson College of Medical, Veterinary & Life Sciences Institute of Molecular Cell and Systems Biology University of Glasgow June 2011 © Ross Thomson 2011 2 Abstract Methylation of CpG dinucleotides is the major epigenetic modification of mammalian DNA which results in the remodelling of transcriptionally active euchromatin to transcriptionally inactive heterochromatin. Recognition of methylated CpG by methylated DNA binding proteins, the MBD family, the Kaiso zinc finger family and the SRA domain proteins results in deacetylation and methylation of histone side chains through the recruitment of HDAC and HMT enzymes. Methylation of DNA is a heritable process ensuring Methylation dependant transcriptional repression is passed from mother to daughter cell during replication. Some of the proteins involved in this chromatin remodelling, MBD1, DNMT1, MLL, and CFP1 contain CXXC domains. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Specificity, Propagation, and Memory of Pericentric Heterochromatin
Article Specificity, propagation, and memory of pericentric heterochromatin Katharina Müller-Ott1, Fabian Erdel1, Anna Matveeva2, Jan-Philipp Mallm1, Anne Rademacher1, Matthias Hahn3, Caroline Bauer1, Qin Zhang2, Sabine Kaltofen1,†, Gunnar Schotta3, Thomas Höfer2 & Karsten Rippe1,* Abstract (Berger et al, 2009). These chromatin signals in turn recruit archi- tectural chromatin components or chromatin remodeling factors in The cell establishes heritable patterns of active and silenced chro- a highly dynamic manner and regulate genome access (McBryant matin via interacting factors that set, remove, and read epigenetic et al, 2006; Taverna et al, 2007; Campos & Reinberg, 2009; Clapier marks. To understand how the underlying networks operate, we & Cairns, 2009; Erdel et al, 2011a). On a global scale, the concerted have dissected transcriptional silencing in pericentric heterochro- and targeted activity of these networks results in the formation of matin (PCH) of mouse fibroblasts. We assembled a quantitative the denser, transcriptionally repressed heterochromatin state and map for the abundance and interactions of 16 factors related to the more open and biologically active euchromatin, which can be PCH in living cells and found that stably bound complexes of the distinguished at the resolution of the light microscope (Grewal & histone methyltransferase SUV39H1/2 demarcate the PCH state. Jia, 2007; Eissenberg & Reuter, 2009). A prototypic example for a From the experimental data, we developed a predictive mathe- constitutive heterochromatin domain is pericentric heterochromatin matical model that explains how chromatin-bound SUV39H1/2 (PCH) in mouse cells (Probst & Almouzni, 2008). It is characterized complexes act as nucleation sites and propagate a spatially by its high content of repetitive major satellite repeats and repres- confined PCH domain with elevated histone H3 lysine 9 trimethyla- sive epigenetic marks such as 5-methylcytosine (5meC) the binding tion levels via chromatin dynamics. -
Genome-Wide DNA Methylation Analysis Reveals Molecular Subtypes of Pancreatic Cancer
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 17), pp: 28990-29012 Research Paper Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer Nitish Kumar Mishra1 and Chittibabu Guda1,2,3,4 1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA 2Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA 3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA 4Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA Correspondence to: Chittibabu Guda, email: [email protected] Keywords: TCGA, pancreatic cancer, differential methylation, integrative analysis, molecular subtypes Received: October 20, 2016 Accepted: February 12, 2017 Published: March 07, 2017 Copyright: Mishra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients. -
CXXC1 Polyclonal Antibody - Classic
CXXC1 polyclonal antibody - Classic Other name: CFP1, CGBP, PCCX1, PHF18, SPP1, ZCGPC1 Cat. No. C15410315 Specificity: Human: positive / Other species: not tested Type: Polyclonal ChIP-grade / ChIP-seq-grade Purity: Affinity purified polyclonal antibody in PBS containing Source: Rabbit 0.02% azide and 50% glycerol. Lot #: 001 Storage: Store at -20°C; for long storage, store at -80°C Avoid multiple freeze-thaw cycles Size: 50 μg /50 μl Precautions: This product is for research use only Concentration: 1 μg/μl Not for use in diagnostic or therapeutic procedures Description : Polyclonal antibody raised in rabbit against human CXXC1 (CXXC Finger Protein 1), using a recombinant protein. Applications Applications Suggested dilution/amount Results ChIP* 2 μg/ChIP Fig 1, 2 Western blotting 1:1,000 Fig 3 IF 1:100 Fig 4 * Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 1-5 μl per IP. Target description CXXC1 (UniProt/Swiss-Prot entry Q9POU4) is a transcriptional activator that specifically recognizes unmethylated CpG motifs in DNA with a preference for CpGG. The protein contains a CXXC motif in it’s DNA-binding domain. 1 Results Figure 1. ChIP results obtained with the Diagenode antibody directed against CXXC1 ChIP assays were performed using HeLa cells, the Diagenode antibody against CXXC1 (Cat. No. C15410315) and optimized PCR primer sets for qPCR. ChIP was performed with the “iDeal ChIP-seq” kit (Cat. No. C01010055), using sheared chromatin from 4 million cells. A titration consisting of 1, 2 and 5 μg of antibody per ChIP experiment was analyzed. -
H19 Lncrna Controls Gene Expression of the Imprinted Gene Network by Recruiting MBD1
H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1 Paul Monniera,b, Clémence Martineta, Julien Pontisc, Irina Stanchevad, Slimane Ait-Si-Alic, and Luisa Dandoloa,1 aGenetics and Development Department, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8104, University Paris Descartes, Institut Cochin, Paris 75014, France; bUniversity Paris Pierre and Marie Curie, Paris 75005, France; cUniversity Paris Diderot, Sorbonne Paris Cité, Laboratoire Epigénétique et Destin Cellulaire, CNRS UMR 7216, Paris 75013, France; and dWellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom Edited by Marisa Bartolomei, University of Pennsylvania, Philadelphia, PA, and accepted by the Editorial Board November 11, 2013 (received for review May 30, 2013) The H19 gene controls the expression of several genes within the this control is transcriptional or posttranscriptional and whether Imprinted Gene Network (IGN), involved in growth control of the these nine targets are direct or indirect targets remain elusive. embryo. However, the underlying mechanisms of this control re- Several lncRNAs interact with chromatin-modifying com- main elusive. Here, we identified the methyl-CpG–binding domain plexes and appear to exert a transcriptional control by targeting fi protein 1 MBD1 as a physical and functional partner of the H19 local chromatin modi cations at discrete genomic regions (8, 9). long noncoding RNA (lncRNA). The H19 lncRNA–MBD1 complex is In the case of imprinted clusters, the DMRs controlling the ex- fi pression of imprinted genes exhibit parent-of-origin epigenetic required for the control of ve genes of the IGN. -
Essential Genes Shape Cancer Genomes Through Linear Limitation of Homozygous Deletions
ARTICLE https://doi.org/10.1038/s42003-019-0517-0 OPEN Essential genes shape cancer genomes through linear limitation of homozygous deletions Maroulio Pertesi1,3, Ludvig Ekdahl1,3, Angelica Palm1, Ellinor Johnsson1, Linnea Järvstråt1, Anna-Karin Wihlborg1 & Björn Nilsson1,2 1234567890():,; The landscape of somatic acquired deletions in cancer cells is shaped by positive and negative selection. Recurrent deletions typically target tumor suppressor, leading to positive selection. Simultaneously, loss of a nearby essential gene can lead to negative selection, and introduce latent vulnerabilities specific to cancer cells. Here we show that, under basic assumptions on positive and negative selection, deletion limitation gives rise to a statistical pattern where the frequency of homozygous deletions decreases approximately linearly between the deletion target gene and the nearest essential genes. Using DNA copy number data from 9,744 human cancer specimens, we demonstrate that linear deletion limitation exists and exposes deletion-limiting genes for seven known deletion targets (CDKN2A, RB1, PTEN, MAP2K4, NF1, SMAD4, and LINC00290). Downstream analysis of pooled CRISPR/Cas9 data provide further evidence of essentiality. Our results provide further insight into how the deletion landscape is shaped and identify potentially targetable vulnerabilities. 1 Hematology and Transfusion Medicine Department of Laboratory Medicine, BMC, SE-221 84 Lund, Sweden. 2 Broad Institute, 415 Main Street, Cambridge, MA 02142, USA. 3These authors contributed equally: Maroulio Pertesi, Ludvig Ekdahl. Correspondence and requests for materials should be addressed to B.N. (email: [email protected]) COMMUNICATIONS BIOLOGY | (2019) 2:262 | https://doi.org/10.1038/s42003-019-0517-0 | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-019-0517-0 eletion of chromosomal material is a common feature of we developed a pattern-based method to identify essential genes Dcancer genomes1.