Abstract

Bivalent promoters, that are simultaneously marked by activation- and repression-associated histone modifications, have been proposed to maintain ES cell genes in a poised configuration. During differentiation such promoters resolve to fully active or inactive states, with associated changes in gene expression. Here we followed the fate of bivalent promoters during hematopoietic stem cell (HSC) differentiation to T lymphoid lineage committed cells. We show that HSC bivalents interconverted between monovalent and bivalent chromatin states at sequential developmental stages, with only a minority resolving to either monovalent state for the long-term. Conversely, bivalent promoters that were generated de novo interconverted between precursor states and bivalency. Neither generation nor resolution of bivalency was accompanied by changes in gene expression. Moreover, singly marked genes did not transition to the opposing monovalent state via a bivalent intermediate. Our observations reveal unprecedented dynamics of bivalent chromatin during hematopoiesis that suggests a developmental role beyond poising genes for future resolution.

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