组蛋白H3K4甲基转移酶复合物亚基Ash2参与裂殖酵母产孢

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

在氮源缺乏及信息素存在的条件下,裂殖酵母(Schizosaccharomyces pombe)进行减数分裂并完成产孢。在此过程中,信息素介导的MAPK(Mitogen-activated protein kinases)信号通路调控减数分裂相关基因的表达。Spk1是MAPK通路的核心成员,通过蛋白磷酸化的方式激活转录因子Ste11,从而激活mei2+、mam2+和map3+等减数分裂相关基因的表达。尽管组蛋白H3K4甲基化参与基因转录激活、染色质重塑等诸多生物学过程,但其在裂殖酵母产孢过程中的作用并不清楚。文章通过序列比对,发现裂殖酵母Ash2作为H3K4甲基转移酶复合物COMPASS的亚基具有两个保守的结构域,定位于细胞核内参与H3K4的甲基化修饰。ash2+的缺失引起裂殖酵母在氮源缺乏时产孢过程的延迟及产孢率下降。ChIP、定量PCR分析结果显示,ash2+的缺失降低了spk1+编码区H3K4的二甲基化水平,造成spk1+mRNA水平的明显下调。在ash2Δ细胞中,虽然ste11+的转录水平没有变化,但Ste11的靶基因mei2+、mam2+和map3+的转录水平明显下降。在裂殖酵母中,组蛋白H3K4甲基转移酶复合物COMPASS的亚基Ash2通过调控二甲基化水平修饰从而调节MAPK信号通路,参与裂殖酵母的有性生殖,为建立表观遗传修饰与减数分裂之间的联系提供了新的线索。

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 Stell 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 ofspk1＋,as well as a reduction of its mRNA level.Although the mRNA level of stell＋ kept unchanged,the levels of Stell-targetted genes,such as mei2＋,mam2＋ and map3＋,all reduced in ash2△ 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.