In embryonic stem cells (ESCs), bivalency characterizes the chromatin state of developmental gene promoters, simultaneously modified by Mll2 and Polycomb complexes. Despite its essential role in embryogenesis, the function of bivalency is currently unclear. Here we show that Mll2 plays a central role in stem cell genome organization. We generate a catalog of bona-fide bivalent genes in mESCs and demonstrate that loss of Mll2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility and long-range interactions become redistributed, affecting ESC differentiation. We propose that bivalency balances accessibility and long-range connectivity of promoters to modulate developmental gene expression. SOURCE: Enrique Blanco (enrique.blanco@crg.eu) - Epigenetic Events in Cancer (L. Di Croce's lab) Center for Genomic Regulation (CRG)

Pluto Bioinformatics

GSE99530: Promoter bivalency favors an open architecture of the stem cell genome