Further molecular and genetic analysis of upSET, the MLL5 orthologue in D. melanogaster

Several histone methyltransferases are products of the MLL (Mixed Lineage Leukemia) family of genes. Although their mechanisms of action remain elusive, these genes are important because they are often deleted in patients with certain types of leukemia. In most cases, MLLs function catalytically via their SET domains, and their modifications of histones are important for chromatin structure and gene regulation. Here I report my analysis of the fly orthologue of MLL5, upSET. In contrast to an earlier study, RNAi inhibition of upSET gene expression did not result in female sterility but was instead lethal. Although UpSET has a SET domain, down-regulation of upSET does not affect global H3K4-methyl levels. Unlike human MLL5, the SET domain of UpSET does not appear to be an OGT substrate. Additionally, I have characterized UpSET as a suppressor of variegation; this suggests that UpSET is involved in establishment and/or maintenance of chromatin structure and accessibility.