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Developmental Competence Encoded at the Level of Enhancers

ABSTRACT: The emergence of distinct cell types during embryonic development relies on the ability of progenitor cells to properly interpret environmental cues; yet how this developmental competence is established is unknown. Here we show that epigenetic priming of enhancers signifies developmental competence. Chromatin mapping during endodermal lineage diversification of human pluripotent stem cells revealed en masse acquisition of a poised chromatin state at enhancers for multiple descendant lineages in developmental intermediates. The responsiveness of developmental intermediates to lineage-inductive signals is dependent on a poised enhancer state. We further find that lineage-specific enhancers are first recognized by transcription factors involved in chromatin priming, while subsequent recruitment of lineage-inductive transcription factors leads to enhancer and target gene activation. Together, our results identify acquisition of a poised chromatin state at enhancers as a general mechanism by which progenitor cells gain the competence to rapidly activate lineage-specific genes in response to inductive signals.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54471 | GEO | 2015/03/31

SECONDARY ACCESSION(S): PRJNA236597

REPOSITORIES: GEO

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