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

Anna Mattout, Yair Aaronson, Badi Sri Sailaja, Edupuganti V. Raghu Ram, Arigela Harikumar, Jan Philipp Mallm, Kae Hwan Sim, Malka Nissim-Rafinia, Emmanuelle Supper, Prim B. Singh, Siu Kwan Sze, Susan M. Gasser, Karsten Rippe, Eran Meshorer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


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 HP1aα, 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.

Original languageAmerican English
Article number213
JournalGenome Biology
Issue number1
StatePublished - 28 Sep 2015

Bibliographical note

Funding Information:
We thank Thomas Jenuwein (Freiburg) for kindly providing H3K9me3 antibodies; Marc Bühler (Basel) for critical reading of the manuscript; Leah Goodstein and Ravit Netzer (Jerusalem) for help with experiments; all lab members and neighbor colleagues for kind discussion and advice. This work was supported by a postdoctoral fellowship and project grant from the Israel Cancer Research Foundation ICRF (to A.M.) and by grants from the Israel Science Foundation (ISF 1252/12 and 657/12 to E.M.); the Israel Ministry of Science (infrastructure grant to E.M.) and the DKFZ-MOST (CA146) collaboration grant (to K.R. and E.M.) and the European Research Council (ERC-281781 to E.M.).

Publisher Copyright:
© 2015 Mattout et al.


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