Ash2, a subunit of histone H3K4 methyltransferase complex, is involved in the sporulation in Schizosaccharomyces pombe

Abstract

Schizosaccharomyces pombe undergoes meiosis instead of mitosis under conditions of nitrogen starvation and pheromone signalling, which results in conjugation and sporulation. During this progress, the pheromone-responsive MAPK(Mitogen-activated protein kinases) pathway plays an important role in regulating the conjuation and the transcriptional activation of genes required for meiosis. Spk1, a key component of MAPK pathway, activates Ste11 through protein phosphorylation and then induced the transcriptions of several genes requied for meiosis, including mei2(+), mam2(+) and map3(+). Methylation of histone H3K4 is involved in several important biological processes, including transcriptional activation and chromatin remodeling. However, its role in the sporualtion of fission yeast is poorly understood. Ash2 is a subunit of COMPASS, a conserved H3K4 methyltransferase complex. Sequence alignment analysis revealed that Ash2 in pombe shares two conserved domain with other homologues. Ash2 is localized in nucleus and contributes to methylation of H3K4. Deletion of ash2(+) resulted in a delay of sporulation and a substantial drop of sporulation efficiency. ChIP and qPCR analysis showed that deletion of ash2(+) caused a reduction of H3K4me2 level in the coding region of spk1(+), as well as a reduction of its mRNA level. Although the mRNA level of ste11(+) kept unchanged, the levels of Ste11-targetted genes, such as mei2(+), mam2(+) and map3(+), all reduced in ash2Δ cells. The results suggest that Ash2 regulates MAPK pathway and sporulation through H3K4 methylation. This might provide a new clue to elucidate the link between meiosis and epigenetic regulation.