title: Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
abstract: BACKGROUND
  Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown.
  
  
  RESULTS
  Here we identify Heterochromatin Protein 1β (HP1β) as an essential protein for proper differentiation, and, unexpectedly, for the maintenance of pluripotency in ESCs. In pluripotent and differentiated cells HP1β is differentially localized and differentially associated with chromatin. Deletion of HP1β, but not HP1α, in ESCs provokes a loss of the morphological and proliferative characteristics of embryonic pluripotent cells, reduces expression of pluripotency factors and causes aberrant differentiation. However, in differentiated cells, loss of HP1β has the opposite effect, perturbing maintenance of the differentiation state and facilitating reprogramming to an induced pluripotent state. Microscopy, biochemical fractionation and chromatin immunoprecipitation reveal a diffuse nucleoplasmic distribution, weak association with chromatin and high expression levels for HP1β in ESCs. The minor fraction of HP1β that is chromatin-bound in ESCs is enriched within exons, unlike the situation in differentiated cells, where it binds heterochromatic satellite repeats and chromocenters.
  
  
  CONCLUSIONS
  We demonstrate an unexpected duality in the role of HP1β: it is essential in ESCs for maintaining pluripotency, while it is required for proper differentiation in differentiated cells. Thus, HP1β function both depends on, and regulates, the pluripotent state.
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.|Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Mattout
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Yair
authors.initials: Y
authors.lastname: Aaronson
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Badi Sri
authors.initials: BS
authors.lastname: Sailaja
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Edupuganti V
authors.initials: EV
authors.lastname: Raghu Ram
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Arigela
authors.initials: A
authors.lastname: Harikumar
authors.affiliation: Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Jan-Philipp
authors.initials: JP
authors.lastname: Mallm
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, Singapore.
authors.forename: Kae Hwan
authors.initials: KH
authors.lastname: Sim
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Malka
authors.initials: M
authors.lastname: Nissim-Rafinia
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Supper
authors.affiliation: Present address: Department of Natural Sciences and Psychology, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
authors.forename: Prim B
authors.initials: PB
authors.lastname: Singh
authors.affiliation: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, Singapore.
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gasser
authors.affiliation: Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Rippe
authors.affiliation: Department of Genetics, The Institute of Life Science and The Edmond and Lily Center for Brain Sciences The Hebrew University of Jerusalem, Jerusalem, 91904, Israel. meshorer@huji.ac.il.
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics*; D053595:Embryonic Stem Cells; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D057026:Induced Pluripotent Stem Cells; D051379:Mice; D018345:Mice, Knockout
chemical_list: C096188:Cbx1 protein, mouse; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones