组蛋白H3K4甲基转移酶复合物亚基Ash2参与裂殖酵母产孢

doi:10.3724/SP.J.1005.2014.0943

遗传 ›› 2014, Vol. 36 ›› Issue (9): 943-951.doi: 10.3724/SP.J.1005.2014.0943

组蛋白H3K4甲基转移酶复合物亚基Ash2参与裂殖酵母产孢

王文超^{1, 2}, 周欢^{1, 2}, 余垚^{1, 2}, 吕红^{1, 2}

1. 复旦大学生命科学学院,遗传工程国家重点实验室,上海 2004332. 上海市工业菌株工程技术研究中心,上海 200433

收稿日期:2014-04-01 出版日期:2014-09-20 发布日期:2014-09-20
通讯作者: 吕红,博士,教授,研究方向：微生物遗传学。E-mail：honglv@fudan.edu.cn E-mail:11210700068@fudan.edu.cn
作者简介:王文超,硕士研究生,专业方向：微生物分子遗传学。
基金资助:
国家重点基础研究发展计划(973计划)项目(编号：2009CB825601),国家自然科学基金项目(编号：31200961),高等学校博士学科点专项科研基金项目(编号：20120071120010)和上海市科委基地建设项目(编号：13DZ2252000)资助

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

Wenchao Wang^{1, 2}, Huan Zhou^{1, 2}, Yao Yu^{1, 2}, Hong Lv^{1, 2}

1. State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai 200433, China2. Shanghai Engineering Research Center of Industrial Microorganisms Fudan University, Shanghai 200433, China

Received:2014-04-01 Online:2014-09-20 Published:2014-09-20

摘要/Abstract

摘要： 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。

关键词: 裂殖酵母, H3K4甲基化, Ash2, 产孢, MAPK

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.

Key words: H3K4 methylation, Ash2, sporulation, MAPK

王文超, 周欢, 余垚, 吕红. 组蛋白H3K4甲基转移酶复合物亚基Ash2参与裂殖酵母产孢[J]. 遗传, 2014, 36(9): 943-951.

Wenchao Wang, Huan Zhou, Yao Yu, Hong Lv. Ash2, a subunit of histone H3K4 methyltransferase complex, is involved in the sporulation in Schizosaccharomyces pombe[J]. HEREDITAS(Beijing), 2014, 36(9): 943-951.

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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

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