DNA甲基化
卵泡期
DNMT1型
小RNA
细胞生物学
甲基化
生物
细胞凋亡
癌症研究
下调和上调
转录因子
基因表达
基因
内分泌学
遗传学
作者
Xiaofeng Zhou,Yingting He,Xiangchun Pan,Hongyan Quan,Bo He,Yongguang Li,Guofeng Bai,Nian Li,Zhe Zhang,Hao Zhang,Jiaqi Li,Xiaolong Yuan
标识
DOI:10.1038/s41418-022-01103-y
摘要
DNA methylation and long noncoding RNAs (lncRNAs) exhibit an indispensable role in follicular development. However, the specific mechanisms regarding lncRNAs mediated by DNA methylation in follicular development remain unclearly. In this study, we found that inhibiting the expression of DNMT1 promoted granulosa cells (GCs) apoptosis to inhibit follicular development. A novel follicular development-associated lncRNA named inhibitory factor of follicular development (IFFD) was mediated by DNMT1 and showed to arrest follicular development by inhibiting GCs proliferation and estrogen (E2) secretion but promoting GCs apoptosis. Mechanistically, the deactivated Cas9-TET1 demonstrated that the hypomethylation in −1261/−1254 region of IFFD promoted the transcription of IFFD by recruiting SP1. IFFD induced the expression of GLI family zinc finger 1 through competitive binding miR-370, thereby up-regulating the expression of CASP3 to promote GCs apoptosis, as well as downregulating the expressions of PCNA and CYP19A1 to inhibit GCs proliferation and E2 secretion. Collectively, DNMT1-mediated IFFD might be a novel target for the regulation of follicular development.
科研通智能强力驱动
Strongly Powered by AbleSci AI