TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.
TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis.
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DOI：
10.1371/journal.pgen.1006128
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发表时间：
2016-06
期刊：
影响因子：
4.5
通讯作者：
Freiman RN
中科院分区：
文献类型：
--
作者：
Grive KJ;Gustafson EA;Seymour KA;Baddoo M;Schorl C;Golnoski K;Rajkovic A;Brodsky AS;Freiman RN
TAF4b是一般转录因子TFIID的性腺富集亚基，其涉及促进小鼠和人类的健康卵巢衰老和女性生育力。为了进一步探讨TAF4b促进卵泡发育的潜在机制，我们分析了多个时间点人胎儿卵巢中的全局基因表达。该计算分析揭示了人TAF4B和减数分裂I的关键调节因子和效应因子（包括SYCP 3、YBX 2、STAG 3和DAZL）的协调表达。为了解决这一分析的功能相关性，我们转向胚胎Taf4b缺陷小鼠卵巢，在那里，我们第一次证明，在前期I进展以及不联会Taf4b缺陷的卵母细胞的严重缺陷。因此，TAF4b占据许多必需的减数分裂和卵子发生调节因子（包括Stra8、Dazl、Figla和Nobox）的近端启动子，并且是它们的适当表达所需的。这些数据揭示了一种新的TAF4b在调节小鼠卵子发生早期减数分裂基因表达程序的功能，并支持存在一个高度保守的TAF4b依赖的基因调控网络，促进小鼠和妇女的早期卵母细胞发育。早期卵子发生的适当调节对于卵巢的长期健康和生育力至关重要，因为雌性哺乳动物（和女性）在出生时拥有有限的卵母细胞库。卵子发生早期的减数分裂过程确保了基因组的完整性和生殖年和未来几十年的染色体分离。我们研究了转录因子TAF4b在减数分裂基因的正确表达和通过前期I的正确进展中的作用。我们已经确定了TAF4b在促进关键减数分裂基因（包括Stra8、Sycp1、Sycp2和Msy2）的适当表达方面的新功能。此外，我们已经证明了在Figla、Nobox和Dazl的近端启动子处的TAF4b占据。这种占据对于前期I的染色体事件是至关重要的，因为Taf4b缺陷的卵母细胞在减数分裂I中经历缺陷，不联会的高发生率和重组中断。这些数据确定TAF4b作为一种新的上游转录调节因子的早期减数分裂程序，是健康的卵子发生所必需的。
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. Proper regulation of early oogenesis is essential for long-term ovarian health and fertility, as female mammals (and women) possess a finite pool of oocytes at birth. Meiotic progression during these early stages of oogenesis ensures genomic integrity and proper chromosome segregation in the reproductive years and decades to come. We investigated the role of transcription factor TAF4b in proper expression of meiosis genes and in the proper progression through prophase I. We have identified a novel function for TAF4b in promoting appropriate expression of critical meiosis genes including Stra8, Sycp1, Sycp2, and Msy2. Furthermore, we have demonstrated TAF4b occupancy at the proximal promoters of Figla, Nobox, and Dazl. This occupancy is crucial for the chromosomal events of prophase I, as Taf4b-deficent oocytes experience defects in meiosis I, a high incidence of asynapsis, and disrupted recombination. These data identify TAF4b as a novel upstream transcriptional regulator of the early meiotic program that is essential for healthy oogenesis.