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ES cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression.

American Society of Hematology
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  • Biology


Many lineage-specific developmental regulator genes are transcriptionally primed in ES cells; RNA Pol(II) is bound at their promoters but is prevented from productive elongation by the activity of Polycomb Repressive Complexes (PRC) 1 and 2. This epigenetically poised state is thought to enable ES cells to rapidly execute multiple differentiation programs and is recognised by a simultaneous enrichment for H3K4me3 and H3K27me3 modifications (bivalent chromatin) across promoter regions. Here we show that the chromatin profile of this important cohort of genes is progressively modified as ES cells differentiate towards blood-forming precursors. Surprisingly however, neural specifying genes such as Nkx2-2, Nkx2-9 and Sox1 remain bivalent and primed even in committed hemangioblasts, as conditional deletion of PRC1 results in overt and inappropriate expression of neural genes in hemangioblasts. These data reinforce the importance of PRC1 for normal hematopoietic differentiation and reveal an unexpected epigenetic plasticity of mesoderm-committed hemangioblasts.

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