Abstract
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.
Highlights
One of the most fundamental aspects of germline regulation is meiotic progression, in which germ cell chromatin acquires a new configuration [1], genetic material is exchanged between homologous chromosomes, and germ cells are reduced to half the genetic material of the parental cell [2]
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 Stimulated by Retinoic Acid 8 (Stra8), Sycp1, Sycp2, and Msy2
Summary
One of the most fundamental aspects of germline regulation is meiotic progression, in which germ cell chromatin acquires a new configuration [1], genetic material is exchanged between homologous chromosomes, and germ cells are reduced to half the genetic material of the parental cell [2]. Meiotic onset occurs in human oocytes within the fetal human ovary around gestational weeks 11–12, after which diplotene arrest begins around 16–20 weeks [8,9,10] These arrested oocytes remain in diplotene until the first meiotic division just prior to ovulation [7], which will not occur until months later in mice and decades later in humans. In women, these oocytes may not be utilized for conception until four to five decades after their initial formation and arrest. These early embryonic meiotic events must take place with great fidelity, but must ensure long-term genomic integrity to confer proper fertilization and development
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