title: Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment.
abstract: 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.
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooper
authors.affiliation: CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Dienstbier
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Raihann
authors.initials: R
authors.lastname: Hassan
authors.affiliation: Advanced Cellular Imaging, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schermelleh
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.affiliation: Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Neil P
authors.initials: NP
authors.lastname: Blackledge
authors.affiliation: MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Marco
authors.affiliation: Nuclear Dynamics, Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Elderkin
authors.affiliation: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Chromatin Biology and Transcription, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Klose
authors.affiliation: CGAT, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heger
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. Electronic address: neil.brockdorff@bioch.ox.ac.uk.
authors.forename: Neil
authors.initials: N
authors.lastname: Brockdorff
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054875:Ubiquitination
chemical_list: D006570:Heterochromatin; D006657:Histones; D063151:Polycomb Repressive Complex 2