Mrg15 allosterically activates Ash1's H3K36 methyltransferase activity and facilitates Ash1's trithorax group protein function in Drosophila

Ash1 is a classic Trithorax group protein possessing an H3K36-specific histone methyltransferase activity. Ash1 plays a critical role in antagonizing Polycomb silencing and its loss-of-function mutations lead to inactivation of certain Hox genes and homeotic transformation. Here, we report the purification of Ash1 complex with the identification of two novel subunits, Mrg15 and Nurf55. Interestingly, Mrg15 stimulates the enzymatic activity of Ash1 in vitro, and such stimulation is independent of the chromo domain of Mrg15. In vivo, Mrg15 is recruited by Ash1 to their common target genes and Mrg15 is essential for the proper deposition of H3K36me2 at these regions. Overall design: We measured Ash1/Mrg15 genomic binding by ChIP-seq in fly S2 cell lines with WT, siAsh1 and siMrg15 conditions, respectively. Expression profiles by RNA-seq were also done in WT, siAsh1 and siMrg15 S2 cells.