Ji, F.; Kundu, S.; Anselmo, A.; Morris, A.; Ducasse, A.; Ergun, A.; Kingston, R. E.; Sadreyev, R.

The presence of histone modifications associated with both transcriptional repression (H3K27me3) and activation (H3K4me3) on key developmental promoters in embryonic stem cells results from the co-localization of repressive Polycomb group (PcG) and activating Trithorax group (TrxG) protein complexes. Functional interactions between PcG and TrxG on these promoters are not fully understood. Here we focus on the relationships between Fbxl10/Kdm2b, a component of a PcG complex PRC1, and Kmt2b/Mll2, an essential component of TrxG at bivalent promoters. Computational analysis of previously published data revealed genome-wide correlation between chromatin occupancies of these two proteins, suggesting potential crosstalk between Kdm2b and Mll2 at both active and repressed promoters. We tested this hypothesis experimentally and found that loss of Kdm2b resulted in depletion of Mll2 at promoters genome-wide, suggesting that Kdm2b is required for Mll2 occupancy at both bivalent and active promoters. Loss of Kdm2b or the core PRC1 component Ring1b also resulted in the reduction of H3K4me3 specifically at bivalent promoters. These findings provide a direct pathway for cooperation between PcG and TrxG at bivalent promoters, suggesting an unexpected modification to the current model of bivalency. In addition, these findings reveal genome-wide role of Kdm2b independent of the full PRC1 complex.