title: Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
abstract: Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3), respectively. Compared to H3K27me3, localization and the role of H2AK119u1 are not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.
authors: Laboratory for Developmental Genetics, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan. mendoh@rcai.riken.jp
authors: Mitsuhiro
authors: M
authors: Endoh
authors: Takaho A
authors: TA
authors: Endo
authors: Tamie
authors: T
authors: Endoh
authors: Kyo-ichi
authors: K
authors: Isono
authors: Jafar
authors: J
authors: Sharif
authors: Osamu
authors: O
authors: Ohara
authors: Tetsuro
authors: T
authors: Toyoda
authors: Takashi
authors: T
authors: Ito
authors: Ragnhild
authors: R
authors: Eskeland
authors: Wendy A
authors: WA
authors: Bickmore
authors: Miguel
authors: M
authors: Vidal
authors: Bradley E
authors: BE
authors: Bernstein
authors: Haruhiko
authors: H
authors: Koseki
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics
chemical_list: D002843:Chromatin; D006657:Histones; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D011495:Histone-Lysine N-Methyltransferase; D063150:Polycomb Repressive Complex 1; C489840:Ring1 protein, mouse; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases