Grive Kathryn J, Gustafson Eric A, Seymour Kimberly A, Baddoo Melody, Schorl Christoph, Golnoski Kayla, Rajkovic Aleksandar, Brodsky Alexander S, Freiman Richard N
MCB Graduate Program, Brown University, Providence, Rhode Island, United States of America.
MCB Department, Brown University, Providence, Rhode Island, United States of America.
PLoS Genet. 2016 Jun 24;12(6):e1006128. doi: 10.1371/journal.pgen.1006128. eCollection 2016 Jun.
TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women.
TAF4b是通用转录因子TFIID中一种在性腺中高度富集的亚基,在促进小鼠和人类健康的卵巢衰老及女性生育能力方面发挥作用。为了进一步探究TAF4b促进卵巢卵泡发育的潜在机制,我们分析了人类胎儿卵巢多个时间点的全基因组表达情况。该计算分析揭示了人类TAF4B与减数分裂I的关键调节因子和效应因子(包括SYCP3、YBX2、STAG3和DAZL)的协同表达。为了探讨这一分析的功能相关性,我们研究了胚胎期Taf4b基因缺失的小鼠卵巢,首次证明Taf4b基因缺失的卵母细胞在减数分裂前期I进程中存在严重缺陷以及联会紊乱。相应地,TAF4b占据了许多减数分裂和卵子发生关键调节因子(包括Stra8、Dazl、Figla和Nobox)的近端启动子区域,并且是它们正常表达所必需的。这些数据揭示了TAF4b在调节小鼠早期卵子发生过程中减数分裂基因表达程序方面的新功能,并支持存在一个高度保守的、依赖TAF4b的基因调控网络促进小鼠和女性早期卵母细胞发育。