Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/81001 http://hdl.handle.net/10220/39029 |
| _version_ | 1811684584963702784 |
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| author | 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 |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences 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 |
| author_sort | Mattout, Anna |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T04:30:58Z |
| format | Journal Article |
| id | ntu-10356/81001 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:30:58Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/810012023-02-28T16:59:33Z 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 School of Biological Sciences 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. Published version 2015-12-10T06:25:47Z 2019-12-06T14:19:18Z 2015-12-10T06:25:47Z 2019-12-06T14:19:18Z 2015 Journal Article Mattout, A., Aaronson, Y., Sailaja, B. S., Raghu Ram, E. V., Harikumar, A., Mallm, J.-P., et al. (2015). Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells. Genome Biology, 16, 213-. 1465-6906 https://hdl.handle.net/10356/81001 http://hdl.handle.net/10220/39029 10.1186/s13059-015-0760-8 26415775 en Genome Biology © 2015 Mattout et al. Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. 21 p. application/pdf |
| spellingShingle | 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 |
| title | Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| title_full | Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| title_fullStr | Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| title_full_unstemmed | Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| title_short | Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| title_sort | heterochromatin protein 1β hp1β has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells |
| url | https://hdl.handle.net/10356/81001 http://hdl.handle.net/10220/39029 |
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