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

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)213
JournalGenome Biology
Volume16
DOIs
Publication statusPublished - Sep 28 2015
Externally publishedYes

Fingerprint

heterochromatin
Embryonic Stem Cells
Chromatin
protein
embryonic stem cells
chromatin
stem
proteins
cells
Proteins
Maintenance
heterochromatin-specific nonhistone chromosomal protein HP-1
distribution
Pluripotent Stem Cells
Heterochromatin
Chromatin Immunoprecipitation
chromocenters
Epigenomics
Microscopy
Exons

Keywords

  • 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
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Mattout, A., Aaronson, Y., Sailaja, B. S., Raghu Ram, E. V., Harikumar, A., Mallm, J-P., ... Meshorer, E. (2015). Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells. Genome Biology, 16, 213. https://doi.org/10.1186/s13059-015-0760-8

Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells. / Mattout, Anna; Aaronson, Yair; Sailaja, Badi Sri; Raghu Ram, Edupuganti V; Harikumar, Arigela; Mallm, Jan-Philipp; Sim, Kae Hwan; Nissim-Rafinia, Malka; Supper, Emmanuelle; Singh, Prim B; Sze, Siu Kwan; Gasser, Susan M; Rippe, Karsten; Meshorer, Eran.

In: Genome Biology, Vol. 16, 28.09.2015, p. 213.

Research output: Contribution to journalArticle

Mattout, A, Aaronson, Y, Sailaja, BS, Raghu Ram, EV, Harikumar, A, Mallm, J-P, Sim, KH, Nissim-Rafinia, M, Supper, E, Singh, PB, Sze, SK, Gasser, SM, Rippe, K & Meshorer, E 2015, 'Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells', Genome Biology, vol. 16, pp. 213. https://doi.org/10.1186/s13059-015-0760-8
Mattout, Anna ; Aaronson, Yair ; Sailaja, Badi Sri ; Raghu Ram, Edupuganti V ; Harikumar, Arigela ; Mallm, Jan-Philipp ; Sim, Kae Hwan ; Nissim-Rafinia, Malka ; Supper, Emmanuelle ; Singh, Prim B ; Sze, Siu Kwan ; Gasser, Susan M ; Rippe, Karsten ; Meshorer, Eran. / Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells. In: Genome Biology. 2015 ; Vol. 16. pp. 213.
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AU - Mattout, Anna

AU - Aaronson, Yair

AU - Sailaja, Badi Sri

AU - Raghu Ram, Edupuganti V

AU - Harikumar, Arigela

AU - Mallm, Jan-Philipp

AU - Sim, Kae Hwan

AU - Nissim-Rafinia, Malka

AU - Supper, Emmanuelle

AU - Singh, Prim B

AU - Sze, Siu Kwan

AU - Gasser, Susan M

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KW - Histones

KW - Induced Pluripotent Stem Cells

KW - Mice

KW - Mice, Knockout

KW - Journal Article

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