Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment
The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methyl...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471400299X |
| _version_ | 1818692706794209280 |
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| author | Sarah Cooper Martin Dienstbier Raihann Hassan Lothar Schermelleh Jafar Sharif Neil P. Blackledge Valeria De Marco Sarah Elderkin Haruhiko Koseki Robert Klose Andreas Heger Neil Brockdorff |
| author_facet | Sarah Cooper Martin Dienstbier Raihann Hassan Lothar Schermelleh Jafar Sharif Neil P. Blackledge Valeria De Marco Sarah Elderkin Haruhiko Koseki Robert Klose Andreas Heger Neil Brockdorff |
| author_sort | Sarah Cooper |
| collection | DOAJ |
| description | The mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs), CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications. |
| first_indexed | 2024-12-17T13:02:03Z |
| format | Article |
| id | doaj.art-f96cf4b32c5e46e8b5eb04672ddb18dd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-17T13:02:03Z |
| publishDate | 2014-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-f96cf4b32c5e46e8b5eb04672ddb18dd2022-12-21T21:47:20ZengElsevierCell Reports2211-12472014-06-01751456147010.1016/j.celrep.2014.04.012Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 RecruitmentSarah Cooper0Martin Dienstbier1Raihann Hassan2Lothar Schermelleh3Jafar Sharif4Neil P. Blackledge5Valeria De Marco6Sarah Elderkin7Haruhiko Koseki8Robert Klose9Andreas Heger10Neil Brockdorff11Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKDevelopmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKAdvanced Cellular Imaging, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, JapanChromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKMRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UKNuclear Dynamics, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UKLaboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, JapanChromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKCGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKDevelopmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UKThe mechanisms by which the major Polycomb group (PcG) complexes PRC1 and PRC2 are recruited to target sites in vertebrate cells are not well understood. Building on recent studies that determined a reciprocal relationship between DNA methylation and Polycomb activity, we demonstrate that, in methylation-deficient embryonic stem cells (ESCs), CpG density combined with antagonistic effects of H3K9me3 and H3K36me3 redirects PcG complexes to pericentric heterochromatin and gene-rich domains. Surprisingly, we find that PRC1-linked H2A monoubiquitylation is sufficient to recruit PRC2 to chromatin in vivo, suggesting a mechanism through which recognition of unmethylated CpG determines the localization of both PRC1 and PRC2 at canonical and atypical target sites. We discuss our data in light of emerging evidence suggesting that PcG recruitment is a default state at licensed chromatin sites, mediated by interplay between CpG hypomethylation and counteracting H3 tail modifications.http://www.sciencedirect.com/science/article/pii/S221112471400299X |
| spellingShingle | Sarah Cooper Martin Dienstbier Raihann Hassan Lothar Schermelleh Jafar Sharif Neil P. Blackledge Valeria De Marco Sarah Elderkin Haruhiko Koseki Robert Klose Andreas Heger Neil Brockdorff Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment Cell Reports |
| title | Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment |
| title_full | Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment |
| title_fullStr | Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment |
| title_full_unstemmed | Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment |
| title_short | Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment |
| title_sort | targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for h2ak119u1 in prc2 recruitment |
| url | http://www.sciencedirect.com/science/article/pii/S221112471400299X |
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