Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation
Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failu...
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| Format: | Article |
| Language: | en_US |
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Public Library of Science
2014
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| Online Access: | http://hdl.handle.net/1721.1/92486 https://orcid.org/0000-0001-7099-1127 https://orcid.org/0000-0003-3491-4962 |
| _version_ | 1811079007963185152 |
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| author | Levine, Stuart S. Thornton, Seraphim R. Butty, Vincent L G Boyer, Laurie Ann |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Levine, Stuart S. Thornton, Seraphim R. Butty, Vincent L G Boyer, Laurie Ann |
| author_sort | Levine, Stuart S. |
| collection | MIT |
| description | Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, making it difficult to determine the precise roles of PRC2 during lineage commitment. Moreover, while studies suggest that PRC2 prevents DNA methylation, how these two epigenetic regulators coordinate to regulate lineage programs is poorly understood. Using several PRC2 mutant ESC lines that maintain varying levels of H3K27me3, we found that partial maintenance of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). In contrast, genes that function to specify other lineages failed to be repressed in these cells, suggesting that PRC2 is also necessary for lineage fidelity. We also found that loss of H3K27me3 leads to a modest gain in DNA methylation at PRC2 target regions in both ESCs and in SMNs. Our study demonstrates a critical role for PRC2 in safeguarding lineage decisions and in protecting genes against inappropriate DNA methylation. |
| first_indexed | 2024-09-23T11:08:42Z |
| format | Article |
| id | mit-1721.1/92486 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:08:42Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/924862022-09-27T17:26:15Z Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation Levine, Stuart S. Thornton, Seraphim R. Butty, Vincent L G Boyer, Laurie Ann Massachusetts Institute of Technology. Department of Biology Thornton, Sera Butty, Vincent Levine, Stuart S. Boyer, Laurie Polycomb Repressive Complex 2 (PRC2) catalyzes histone H3 lysine 27 tri-methylation (H3K27me3), an epigenetic modification associated with gene repression. H3K27me3 is enriched at the promoters of a large cohort of developmental genes in embryonic stem cells (ESCs). Loss of H3K27me3 leads to a failure of ESCs to properly differentiate, making it difficult to determine the precise roles of PRC2 during lineage commitment. Moreover, while studies suggest that PRC2 prevents DNA methylation, how these two epigenetic regulators coordinate to regulate lineage programs is poorly understood. Using several PRC2 mutant ESC lines that maintain varying levels of H3K27me3, we found that partial maintenance of H3K27me3 allowed for proper temporal activation of lineage genes during directed differentiation of ESCs to spinal motor neurons (SMNs). In contrast, genes that function to specify other lineages failed to be repressed in these cells, suggesting that PRC2 is also necessary for lineage fidelity. We also found that loss of H3K27me3 leads to a modest gain in DNA methylation at PRC2 target regions in both ESCs and in SMNs. Our study demonstrates a critical role for PRC2 in safeguarding lineage decisions and in protecting genes against inappropriate DNA methylation. National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051) National Institutes of Health (U.S.) (Training Grant T 32 GM007287) Smith Family Foundation (Contract LTR DATED 11/6/09) 2014-12-23T20:43:48Z 2014-12-23T20:43:48Z 2014-10 2014-04 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/92486 Thornton, Seraphim R., Vincent L. Butty, Stuart S. Levine, and Laurie A. Boyer. “Polycomb Repressive Complex 2 Regulates Lineage Fidelity During Embryonic Stem Cell Differentiation.” Edited by Jason G. Knott. PLoS ONE 9, no. 10 (October 21, 2014): e110498. https://orcid.org/0000-0001-7099-1127 https://orcid.org/0000-0003-3491-4962 en_US http://dx.doi.org/10.1371/journal.pone.0110498 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Levine, Stuart S. Thornton, Seraphim R. Butty, Vincent L G Boyer, Laurie Ann Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title | Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title_full | Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title_fullStr | Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title_full_unstemmed | Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title_short | Polycomb Repressive Complex 2 Regulates Lineage Fidelity during Embryonic Stem Cell Differentiation |
| title_sort | polycomb repressive complex 2 regulates lineage fidelity during embryonic stem cell differentiation |
| url | http://hdl.handle.net/1721.1/92486 https://orcid.org/0000-0001-7099-1127 https://orcid.org/0000-0003-3491-4962 |
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