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TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis

机译:TAF4b调节减数分裂必不可少的卵母细胞特定基因

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摘要

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.
机译:TAF4b是通用转录因子TFIID的富含性腺的亚基,与促进小鼠和人类的健康卵巢衰老和女性生育力有关。为了进一步探讨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局基因表达。这项计算分析揭示了人类TAF4B与减数分裂I的关键调控因子和效应子(包括SYCP3,YBX2,STAG3和DAZL)的协调表达。为了解决此分析的功能相关性,我们转向了缺乏Taf4b的胚胎小鼠卵巢,我们首次证明了前期I进程的严重缺陷以及缺乏Taf4b的卵母细胞的突触。因此,TAF4b占据了许多必需的减数分裂和卵子发生调节因子的近端启动子,包括Stra8,Dazl,Figla和Nobox,并且它们的正确表达是必需的。这些数据揭示了新型TAF4b在早期小鼠卵子形成中调控减数分裂基因表达程序的功能,并支持高度保守的TAF4b依赖性基因调控网络的存在,从而促进小鼠和女性早期卵母细胞的发育。

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