植物组蛋白去甲基化酶MED1调控减数分裂重组的分子机理

Meiosis is essential for eukaryotic sexual reproduction and produces haploid gametes such as sperms and eggs. The effusion of sperm and egg restores to haploid level, thus remaining the genome stability. Unlike mitosis, meiosis includes meiosis I and II, in which meiosis I involves the homologous chromosome (homolog) interaction, including paring, synapsis, recombination and segregation. Chromatin medication such as DNA methylation and histone modification have a great influence on meiotic progression. To date, knowledge for understanding of chromatin modification on plant meiosis is very limited. The applicant group previously analyzed the Arabidopsis meiocyte transcriptome and identified a set of chromatin regulators that are preferentially expressed in meiocytes. Through phenotypic screening of corresponding mutants, we obtained a histone H3K9 demethylase MED1. The med1 mutants showed reduced fertility and formed polyads instead of tetrad, indicative of meiotic defect. Chromosome florescence in situ hybridization results demonstrated that med1 meiocytes involves non-homologous chromosome interaction and reduces the frequency of meiotic crossovers. Further immunofluorescence result supported a defect of axial element in med1. Building on the previous results, this project will fully utilize molecular cell biology and genetics, biochemistry, multi omics and bioinformatics, to in-depth investigate the molecular mechanism of MED1 in regulating meiotic recombination in plants.

减数分裂是真核生物有性生殖必需的环节，通过减数分裂产生单倍体的配子，雌雄配子融合又恢复到二倍体状态，维持了基因组的稳定性。不同于有丝分裂，减数分裂I涉及到同源染色体之间的相互作用，包括配对、联会、重组和分离。染色质的修饰，如DNA甲基化和组蛋白的修饰等会影响同源染色体之间的相互作用，但是迄今植物中该方面的研究相对较少。申请人团队前期获得减数分裂细胞的表达谱，筛选到一批在该细胞中优先表达的染色质修饰因子，结合相应突变体的表型筛查，获得一个组蛋白H3K9去甲基化酶MED1。med1突变体的育性显著降低，存在多分体现象，表明减数分裂异常；染色体原位杂交结果表明ibm1中存在非同源染色体之间相互作用，且重组频率显著降低；免疫荧光结果显示ibm1突变体中轴向元件局部异常。在此基础上，本项目拟综合采用遗传学、细胞学、生物化学、多组学和计算生物学等手段，深入研究MED1调控减数分裂重组的分子机制。

减数分裂是真核生物有性生殖必需的环节，通过减数分裂产生单倍体的配子，雌雄配子融合又恢复到二倍体状态，维持了基因组的稳定性。不同于有丝分裂，减数分裂I涉及到同源染色体之间的相互作用，包括配对、联会、重组和分离。染色质的修饰，如DNA甲基化和组蛋白的修饰等会影响同源染色体之间的相互作用，但是迄今植物中该方面的研究相对较少。本项目主要在以下几个方面取得突出进展：1）揭示了组蛋白H3K9me2去甲基化酶IBM1通过影响基因区表观遗传修饰，从而调控减数分裂相关重要基因表达，进而参与减数分裂的联会和重组过程；2）阐明了减数分裂特异PHD结构域蛋白MMD1通过调控组蛋白去甲基化酶JMJ16的底物特异性，进而作用减数分裂浓缩相关基因的表达，从而影响染色体的浓缩；3）发现了DNA聚合酶epsilon调控减数分裂重组热区基因表达和异染色质形成的表观遗传机制。相关研究成果在Nature Plants、PNAS、Plant Cell等期刊发表论文13篇。这些研究结果不仅加深了对减数分裂基础问题的认识，同时也为人类生殖健康和农作物育种提供理论借鉴。