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Genome Biol. 2015 Sep 28;16:213. doi: 10.1186/s13059-015-0760-8.

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.

Author information

1
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.
2
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland.
3
Research Group Genome Organization & Function, Deutsches Krebsforschungszentrum (DKFZ) and BioQuant, Im Neuenheimer Feld 280, Heidelberg, Germany.
4
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, Singapore.
5
Present address: Department of Natural Sciences and Psychology, Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, UK.
6
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.

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.

PMID:
26415775
PMCID:
PMC4587738
DOI:
10.1186/s13059-015-0760-8
[Indexed for MEDLINE]
Free PMC Article

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