Journal article
Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.
- Mattout A 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.
- Aaronson Y 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.
- Sailaja BS 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.
- Raghu Ram EV 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.
- Harikumar A 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.
- Mallm JP Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, Germany.
- Sim KH School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, Singapore.
- Nissim-Rafinia M 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.
- Supper E 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.
- Singh PB Present address: Department of Natural Sciences and Psychology, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
- Sze SK School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, Singapore.
- Gasser SM Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
- Rippe K Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, Germany.
- Meshorer E 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.
- 2015-09-30
Published in:
- Genome biology. - 2015
Animals
Cell Differentiation
Cellular Reprogramming
Chromatin
Chromosomal Proteins, Non-Histone
Embryonic Stem Cells
Gene Expression Regulation, Developmental
Heterochromatin
Histones
Induced Pluripotent Stem Cells
Mice
Mice, Knockout
English
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.
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.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1186/s13059-015-0760-8
- PMID 26415775
- Persistent URL
- https://sonar.ch/global/documents/232467
Statistics
Document views: 19
File downloads: