中文摘要
卵泡是女性生殖能力的决定性因素,卵泡正常发育取决于基因表达的适时开关,而基因表的达适时开关主要通过组蛋白适时的乙酰化和去乙酰化来实现的。我们前期研究发现,在发育期卵泡的卵母细胞中,组蛋白H4K16的乙酰转移酶Mof (males absent on the first) 的表达水平及其相应的底物H4K16的乙酰化水平(H4K16ac)都很高,提示Mof在卵泡发育过程中发挥重要作用,但其具体机制尚不清楚。本项目将以卵母细胞中特异敲除Mof基因的小鼠为模型,利用免疫荧光化学、卵母细胞体外培养、染色质免疫共沉淀等技术研究Mof在卵泡发育过程中的作用,并结合转录组测序、生物信息学分析和CRISPR/CAS9介导的基因修饰小鼠制备等方法,深入探讨Mof基因缺失影响卵泡发育的分子基础,以期阐明Mof调节卵泡发育的分子生物学机理,为卵泡发育障碍引起的不孕症的诊断、治疗,提供科学依据。
英文摘要
Follicle is essential for female fertility. Normal development of follicle lies on genes’ spatio-temporal expression, which is regulated by histone (de)acetylation. In our previous study, acetylated histone H4 at lysine 16 (H4K16ac) and its acetyltransferase Mof (males absent on the first) are highly expressed at the developing follicles, suggesting essential role of Mof-regulated acetylation on follicle development. However, the regulation mechanism is unclear. To explore the role of Mof in the development of follicles, we generated conditional Mof knockout (KO) mice in which Mof was specifically deleted in oocytes. We will employ immunofluorescence analysis, in vitro oocyte culture, transcriptome sequencing and in CRISPR/CAS9 techniques to investigate the role of Mof on follicle development. Our study will uncover new cellular and molecular mechanism of aberrant follicle development and provide scientific evidence for the cure of infertility induced by abnormal follicle development.
