Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
Identifieur interne : 000205 ( Main/Exploration ); précédent : 000204; suivant : 000206Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation
Auteurs : Neil P. Blackledge [Royaume-Uni] ; Anca M. Farcas [Royaume-Uni] ; Takashi Kondo [Japon] ; Hamish W. King [Royaume-Uni] ; Joanna F. Mcgouran [Royaume-Uni] ; Lars L. P. Hanssen [Royaume-Uni] ; Shinsuke Ito [Japon] ; Sarah Cooper [Royaume-Uni] ; Kaori Kondo [Japon] ; Yoko Koseki [Japon] ; Tomoyuki Ishikura [Japon] ; Hannah K. Long [Royaume-Uni] ; Thomas W. Sheahan [Royaume-Uni] ; Neil Brockdorff [Royaume-Uni] ; Benedikt M. Kessler [Royaume-Uni] ; Haruhiko Koseki [Japon] ; Robert J. Klose [Royaume-Uni]Source :
- Cell [ 0092-8674 ] ; 2014.
Abstract
Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. These observations provide a surprising PRC1-dependent logic for PRC2 occupancy at target sites in vivo.
Url:
DOI: 10.1016/j.cell.2014.05.004
PubMed: 24856970
PubMed Central: 4048464
Affiliations:
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Sheahan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Brockdorff, Neil" sort="Brockdorff, Neil" uniqKey="Brockdorff N" first="Neil" last="Brockdorff">Neil Brockdorff</name><affiliation wicri:level="4"><nlm:aff id="aff4">Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Kessler, Benedikt M" sort="Kessler, Benedikt M" uniqKey="Kessler B" first="Benedikt M." last="Kessler">Benedikt M. Kessler</name><affiliation wicri:level="4"><nlm:aff id="aff3">Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Koseki, Haruhiko" sort="Koseki, Haruhiko" uniqKey="Koseki H" first="Haruhiko" last="Koseki">Haruhiko Koseki</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Klose, Robert J" sort="Klose, Robert J" uniqKey="Klose R" first="Robert J." last="Klose">Robert J. Klose</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24856970</idno><idno type="pmc">4048464</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048464</idno><idno type="RBID">PMC:4048464</idno><idno type="doi">10.1016/j.cell.2014.05.004</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000349</idno><idno type="wicri:Area/Pmc/Curation">000349</idno><idno type="wicri:Area/Pmc/Checkpoint">000172</idno><idno type="wicri:Area/Ncbi/Merge">000243</idno><idno type="wicri:Area/Ncbi/Curation">000243</idno><idno type="wicri:Area/Ncbi/Checkpoint">000243</idno><idno type="wicri:doubleKey">0092-8674:2014:Blackledge N:variant:prc:complex</idno><idno type="wicri:Area/Main/Merge">000205</idno><idno type="wicri:Area/Main/Curation">000205</idno><idno type="wicri:Area/Main/Exploration">000205</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation</title><author><name sortKey="Blackledge, Neil P" sort="Blackledge, Neil P" uniqKey="Blackledge N" first="Neil P." last="Blackledge">Neil P. Blackledge</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Farcas, Anca M" sort="Farcas, Anca M" uniqKey="Farcas A" first="Anca M." last="Farcas">Anca M. Farcas</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Kondo, Takashi" sort="Kondo, Takashi" uniqKey="Kondo T" first="Takashi" last="Kondo">Takashi Kondo</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="King, Hamish W" sort="King, Hamish W" uniqKey="King H" first="Hamish W." last="King">Hamish W. King</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Mcgouran, Joanna F" sort="Mcgouran, Joanna F" uniqKey="Mcgouran J" first="Joanna F." last="Mcgouran">Joanna F. Mcgouran</name><affiliation wicri:level="4"><nlm:aff id="aff3">Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Hanssen, Lars L P" sort="Hanssen, Lars L P" uniqKey="Hanssen L" first="Lars L. P." last="Hanssen">Lars L. P. Hanssen</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Ito, Shinsuke" sort="Ito, Shinsuke" uniqKey="Ito S" first="Shinsuke" last="Ito">Shinsuke Ito</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Cooper, Sarah" sort="Cooper, Sarah" uniqKey="Cooper S" first="Sarah" last="Cooper">Sarah Cooper</name><affiliation wicri:level="4"><nlm:aff id="aff4">Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Kondo, Kaori" sort="Kondo, Kaori" uniqKey="Kondo K" first="Kaori" last="Kondo">Kaori Kondo</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Koseki, Yoko" sort="Koseki, Yoko" uniqKey="Koseki Y" first="Yoko" last="Koseki">Yoko Koseki</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Ishikura, Tomoyuki" sort="Ishikura, Tomoyuki" uniqKey="Ishikura T" first="Tomoyuki" last="Ishikura">Tomoyuki Ishikura</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Long, Hannah K" sort="Long, Hannah K" uniqKey="Long H" first="Hannah K." last="Long">Hannah K. Long</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Sheahan, Thomas W" sort="Sheahan, Thomas W" uniqKey="Sheahan T" first="Thomas W." last="Sheahan">Thomas W. Sheahan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Brockdorff, Neil" sort="Brockdorff, Neil" uniqKey="Brockdorff N" first="Neil" last="Brockdorff">Neil Brockdorff</name><affiliation wicri:level="4"><nlm:aff id="aff4">Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Kessler, Benedikt M" sort="Kessler, Benedikt M" uniqKey="Kessler B" first="Benedikt M." last="Kessler">Benedikt M. Kessler</name><affiliation wicri:level="4"><nlm:aff id="aff3">Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Ubiquitin Proteolysis Group, Central Proteomics Facility, Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, OX3 7BN</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author><author><name sortKey="Koseki, Haruhiko" sort="Koseki, Haruhiko" uniqKey="Koseki H" first="Haruhiko" last="Koseki">Haruhiko Koseki</name><affiliation wicri:level="1"><nlm:aff id="aff2">Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Laboratory of Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045</wicri:regionArea><wicri:noRegion>Kanagawa 230-0045</wicri:noRegion></affiliation></author><author><name sortKey="Klose, Robert J" sort="Klose, Robert J" uniqKey="Klose R" first="Robert J." last="Klose">Robert J. Klose</name><affiliation wicri:level="4"><nlm:aff id="aff1">Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Laboratory of Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU</wicri:regionArea><orgName type="university">Université d'Oxford</orgName><placeName><settlement type="city">Oxford</settlement><region type="nation">Angleterre</region><region type="région" nuts="1">Oxfordshire</region></placeName></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><idno type="eISSN">1097-4172</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>Chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. This activity is restricted to variant PRC1 complexes, and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for normal polycomb domain formation and mouse development. 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Blackledge</name></region><name sortKey="Brockdorff, Neil" sort="Brockdorff, Neil" uniqKey="Brockdorff N" first="Neil" last="Brockdorff">Neil Brockdorff</name><name sortKey="Cooper, Sarah" sort="Cooper, Sarah" uniqKey="Cooper S" first="Sarah" last="Cooper">Sarah Cooper</name><name sortKey="Farcas, Anca M" sort="Farcas, Anca M" uniqKey="Farcas A" first="Anca M." last="Farcas">Anca M. Farcas</name><name sortKey="Hanssen, Lars L P" sort="Hanssen, Lars L P" uniqKey="Hanssen L" first="Lars L. P." last="Hanssen">Lars L. P. Hanssen</name><name sortKey="Kessler, Benedikt M" sort="Kessler, Benedikt M" uniqKey="Kessler B" first="Benedikt M." last="Kessler">Benedikt M. Kessler</name><name sortKey="King, Hamish W" sort="King, Hamish W" uniqKey="King H" first="Hamish W." last="King">Hamish W. King</name><name sortKey="Klose, Robert J" sort="Klose, Robert J" uniqKey="Klose R" first="Robert J." last="Klose">Robert J. Klose</name><name sortKey="Long, Hannah K" sort="Long, Hannah K" uniqKey="Long H" first="Hannah K." last="Long">Hannah K. Long</name><name sortKey="Mcgouran, Joanna F" sort="Mcgouran, Joanna F" uniqKey="Mcgouran J" first="Joanna F." last="Mcgouran">Joanna F. Mcgouran</name><name sortKey="Sheahan, Thomas W" sort="Sheahan, Thomas W" uniqKey="Sheahan T" first="Thomas W." last="Sheahan">Thomas W. Sheahan</name></country><country name="Japon"><noRegion><name sortKey="Kondo, Takashi" sort="Kondo, Takashi" uniqKey="Kondo T" first="Takashi" last="Kondo">Takashi Kondo</name></noRegion><name sortKey="Ishikura, Tomoyuki" sort="Ishikura, Tomoyuki" uniqKey="Ishikura T" first="Tomoyuki" last="Ishikura">Tomoyuki Ishikura</name><name sortKey="Ito, Shinsuke" sort="Ito, Shinsuke" uniqKey="Ito S" first="Shinsuke" last="Ito">Shinsuke Ito</name><name sortKey="Kondo, Kaori" sort="Kondo, Kaori" uniqKey="Kondo K" first="Kaori" last="Kondo">Kaori Kondo</name><name sortKey="Koseki, Haruhiko" sort="Koseki, Haruhiko" uniqKey="Koseki H" first="Haruhiko" last="Koseki">Haruhiko Koseki</name><name sortKey="Koseki, Yoko" sort="Koseki, Yoko" uniqKey="Koseki Y" first="Yoko" last="Koseki">Yoko Koseki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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