title: Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment.
abstract: Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, the trophectoderm. We show that a set of somatic lineage regulators (including Hox, Gata and Sox factors) that carry bivalent chromatin enriched in H3K27me3 and H3K4me2 are selectively targeted by Suv39h1-mediated H3K9me3 and de novo DNA methylation in extra-embryonic versus embryonic (pluripotent) lineages, as assessed both in blastocyst-derived stem cells and in vivo. This stably repressed state is linked with a loss of gene priming for transcription through the exclusion of PRC1 (Ring1B) and RNA polymerase II complexes at bivalent, lineage-inappropriate genes upon trophoblast lineage commitment. Collectively, our results suggest a mutually exclusive role for Ring1B and Suv39h1 in regulating distinct chromatin states at key developmental genes and propose a novel mechanism by which lineage specification can be reinforced during early development.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
authors.forename: Olivia
authors.initials: O
authors.lastname: Alder
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lavial
authors.forename: Anne
authors.initials: A
authors.lastname: Helness
authors.forename: Emily
authors.initials: E
authors.lastname: Brookes
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.forename: Anil
authors.initials: A
authors.lastname: Chandrashekran
authors.forename: Philippe
authors.initials: P
authors.lastname: Arnaud
authors.forename: Ana
authors.initials: A
authors.lastname: Pombo
authors.forename: Laura
authors.initials: L
authors.lastname: O'Neill
authors.forename: Véronique
authors.initials: V
authors.lastname: Azuara
mesh_terms: D000818:Animals; D001755:Blastocyst; D019070:Cell Lineage; D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D019175:DNA Methylation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D008780:Methyltransferases / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D063150:Polycomb Repressive Complex 1; D034622:RNA Interference; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D002843:Chromatin; D012097:Repressor Proteins; C498700:Suv39h1 protein, mouse; D008780:Methyltransferases; D063150:Polycomb Repressive Complex 1; C489842:Rnf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D012319:RNA Polymerase II