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 language | English (US) |
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Pages (from-to) | 2483-2492 |
Number of pages | 10 |
Journal | Development |
Volume | 137 |
Issue number | 15 |
DOIs | |
State | Published - Aug 1 2010 |
Externally published | Yes |
Keywords
- Bivalent chromatin
- Early development
- Histone methylation
- Mouse
- Silencing
- Stem cells
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology