Comparison of gene expression changes following knockdown of KMT2A and MSK1 in mouse embryonic fibroblasts

The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET-domain-catalyzed methylation of H3K4. It is essential for normal embryonic development and haematopoiesis and frequently mutated in cancer. The catalytic properties and targeting of KMT2A/MLL1 depend on the proteins with which it complexes and the post-translational protein modifications which some of these proteins put in place, though detailed mechanisms remain unclear. We have shown that KMT2A/MLL1 (both native and FLAG-tagged) and Msk1 (RPS6KA5), co-immunoprecipitated in various cell types. This experiment showed that the great majority of genes whose activity changed on KTM2A/MLL1 knockdown responded comparably to Msk1 knockdown. A 10 array study in which KMT2A (Mll1) or MSK1 were knocked down in mouse embryonic fibroblasts. There were 3 control (mock transfected) samples, 4 KMT2A shRNA samples and 3 MSK1 shRNA samples.