TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis

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. Author Summary 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.