Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment

Olivia Alder, Fabrice Lavial, Anne Helness, Emily Brookes, Sandra Pinho, Anil Chandrashekran, Philippe Arnaud, Ana Pombo, Laura O'Neill, Véronique Azuara

Research output: Contribution to journalArticle

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2483-2492
Number of pages10
JournalDevelopment
Volume137
Issue number15
DOIs
StatePublished - Aug 1 2010

Keywords

  • Bivalent chromatin
  • Early development
  • Histone methylation
  • Mouse
  • Silencing
  • Stem cells

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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    Alder, O., Lavial, F., Helness, A., Brookes, E., Pinho, S., Chandrashekran, A., Arnaud, P., Pombo, A., O'Neill, L., & Azuara, V. (2010). Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development, 137(15), 2483-2492. https://doi.org/10.1242/dev.048363