Biochemical characterization of the human H3K4 methyltransferase complexes

Abstract

Nuclear DNA in eukaryotic cells is organized within a hierarchical chromatin structure that restricts access to regulatory enzymes. Especially, the protruding histone tails are susceptible to posttranslational modifications. Above all, histone H3 lysine 4 (H3K4) methylation is one of the prominent histone modification marks that correlates strongly with active transcription. Mammalian cells have at least six histone H3K4 methyltransferases, thus implicating their possible redundant and unique roles. For biochemical characterization of the human complexes, I reconstituted and purified three full-length and six core complexes following to be subjected in an in vitro histone methyltransferase assay, all complexes exhibit differential H3K4 methyltransferase activity toward free histone H3, indicating all have intrinsic activity. I also found that both SET1A/B complex has the strongest histone H2B ubiquitylation dependent H3K4 methyltransferase activity. These data suggest that human H3K4 complexes have distinctive mechanism of action during H3K4 methylation. More detailed biochemical analyses will help us to understand functions and molecular mechanisms of H3K4 methylation in human.