Promoter bivalency favors an open chromatin architecture in embryonic stem cells
2018
In
embryonic stem cells(ESCs), developmental gene promoters are characterized by their
bivalent chromatinstate, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC
genome organization. We generate a catalog of bona
fidebivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.
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