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

O. Alder (1) , F. Lavial (1) , A. Helness (1) , E. Brookes (2) , S. Pinho (1) , A. Chandrashekran (1) , Philippe P. Arnaud (3) , A. Pombo (2) , L. O'Neill (4) , V. Azuara (1)

1 Hammersmith Hospital NHS Imperial College Healthcare
2 CMBI - MRC Centre for Molecular Microbiology and Infection [Imperial College, London]
3 IGMM - Institut de Génétique Moléculaire de Montpellier
4 University of Birmingham [Birmingham]

Pluripotent cells develop within the inner cell mass of blastocysts, a mosaic of cells surrounded by an extra-embryonic layer, thetrophectoderm. 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 invivo. 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.

Mots clés: Bivalent chromatin; Early development; Histone methylation; Mouse; Silencing; Stem cells; Bivalent chromatin

Domaines: Biochimie, Biologie Moléculaire

O. Alder, F. Lavial, A. Helness, E. Brookes, S. Pinho, et al.. Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment. Development (Cambridge, England), 2010, 137 (15), pp.2483--2492. ⟨10.1242/dev.048363⟩. ⟨hal-02193451⟩