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.
Ring1B and Suv39h1 delineate distinct chromatin states at bivalent genes during early mouse lineage commitment
Alder, O.; Lavial, F.; Helness, A.; Brookes, E.; Pinho, S.; Chandrashekran, A.; Arnaud, P.; Pombo, A.; O'Neill, L.; Azuara, V.
2010-08-01 / vol 137 / pages 2483-92
dev.048363 [pii] 10.1242/dev.048363
1477-9129 (Electronic) 0950-1991 (Linking)
Animals; Mice; DNA Methylation; Models, Biological; RNA Polymerase II/metabolism; *Gene Expression Regulation, Developmental; Blastocyst; Cell Lineage; Chromatin/*chemistry/metabolism; Gene Expression Profiling; Gene Silencing; Methyltransferases/metabolism/*physiology; Repressor Proteins/metabolism/*physiology; RNA Interference; Trophoblasts/metabolism