Set7 is a Novel H3k37 Methyltransferase in Schizosaccharomyces Pombe and Required for Proper Gametogenesis

Abstract

Histone methylation by histone methyltransferases (HMTases) has a key role in transcriptional regulation. Discrepancies between the known HMTases and the histone lysine methylome suggest that novel HMTases remain to be identified. Characterization of new HMTases may clarify transcriptional regulation mechanisms by histone modification. Here we report the discovery, characterization, and crystal structure of Schizosaccharomyces pombe Set7 (SPCC297.04c), a novel and the first identified HMTase methylating the uncharted histone H3 lysine 37 (H3K37) mark. Set7 forms a dimer with its substrate-binding site structurally specific to K37, not the neighboring well-studied K36 mark. We also discovered that H3K37 methylation levels dramatically increase during gametogenesis and defective gametogenesis is observed in set7∆ cells, showing that Set7 and H3K37 methylation play a role in gametogenesis regulation. S. pombe gametogenesis shares similarities with mammalian spermatogenesis and interestingly, we found that Set7 and H3K37 methylation levels affect the processes of gametogenesis. These findings extend our understanding of gametogenesis regulation and support a new link between Set7, H3K37 methylation levels and proper gametogenesis.