title: Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2.
abstract: The Polycomb repressive complexes PRC1 and PRC2 play a central role in developmental gene regulation in multicellular organisms. PRC1 and PRC2 modify chromatin by catalysing histone H2A lysine 119 ubiquitylation (H2AK119u1), and H3 lysine 27 methylation (H3K27me3), respectively. Reciprocal crosstalk between these modifications is critical for the formation of stable Polycomb domains at target gene loci. While the molecular mechanism for recognition of H3K27me3 by PRC1 is well defined, the interaction of PRC2 with H2AK119u1 is poorly understood. Here we demonstrate a critical role for the PRC2 cofactor Jarid2 in mediating the interaction of PRC2 with H2AK119u1. We identify a ubiquitin interaction motif at the amino-terminus of Jarid2, and demonstrate that this domain facilitates PRC2 localization to H2AK119u1 both in vivo and in vitro. Our findings ascribe a critical function to Jarid2 and define a key mechanism that links PRC1 and PRC2 in the establishment of Polycomb domains.
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Cooper
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Grijzenhout
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Underwood
authors.affiliation: Institut Curie, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
authors.forename: Katia
authors.identifier: 0000-0002-2117-9754
authors.initials: K
authors.lastname: Ancelin
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Tatyana B
authors.identifier: 0000-0001-7740-4386
authors.initials: TB
authors.lastname: Nesterova
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Burcu
authors.initials: B
authors.lastname: Anil-Kirmizitas
authors.affiliation: Genome Engineering Oxford, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bassett
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.|Centre for Epigenetics, Ole Maaløes Vej 5, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Kooistra
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.|Centre for Epigenetics, Ole Maaløes Vej 5, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Karl
authors.initials: K
authors.lastname: Agger
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark.|Centre for Epigenetics, Ole Maaløes Vej 5, University of Copenhagen, 2200 Copenhagen, Denmark.|The Danish Stem Cell Center (Danstem), University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
authors.forename: Kristian
authors.identifier: 0000-0003-1975-6097
authors.initials: K
authors.lastname: Helin
authors.affiliation: Institut Curie, CNRS UMR3215, INSERM U934, 26 rue d'Ulm, Paris 75248, France.
authors.forename: Edith
authors.initials: E
authors.lastname: Heard
authors.affiliation: Developmental Epigenetics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Brockdorff
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019175:DNA Methylation; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D054875:Ubiquitination; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D006657:Histones; C093650:Jarid2 protein, mouse; D009707:Nucleosomes; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1; D008239:Lysine