Establishment of a healthy ovarian reserve is contingent upon numerous regulatory pathways during embryogenesis. Previously, mice lacking TBP-associated factor 4b (Taf4b) were shown to exhibit a diminished ovarian reserve. However, potential oocyte-intrinsic functions of TAF4b have not been examined. Here we use a combination of gene expression profiling and chromatin mapping to characterize TAF4b-dependent gene regulatory networks in mouse oocytes. We find that Taf4b-deficient oocytes display inappropriate expression of meiotic, chromatin, and X-linked genes. Furthermore, dysregulated genes in Taf4b-deficient oocytes exhibit an unexpected amount of overlap with dysregulated genes in Turner Syndrome oocytes. Using Cleavage Under Targets and Release Using Nuclease (CUT&RUN), we observed TAF4b enrichment at genes involved in chromatin remodeling and DNA repair, some of which are differentially expressed in Taf4b-deficient oocytes. Interestingly, TAF4b target genes were enriched for Sp/Klf family and NFY target motifs rather than TATA-box motifs, suggesting an alternate mode of promoter interaction. Together, our data connects several gene regulatory nodes that contribute to the precise development of the mammalian ovarian reserve.

Prospermatogonia (ProSpg) link the embryonic development of male primordial germ cells to the healthy establishment of postnatal spermatogonia and long-term mammalian spermatogenesis. While these spermatogenic precursor cells undergo the characteristic transitions of cycling and quiescence, the transcriptional events underlying these developmental hallmarks remain unknown. Here we investigated the expression and function of TAF4b in the timely development of mouse ProSpg using an integration of gene expression profiling and chromatin mapping. We find that Taf4b mRNA expression is elevated during the transition of M-to-T1 ProSpg and Taf4b-deficient ProSpg are delayed in their entry into quiescence. Gene ontology, protein network analysis, and chromatin mapping demonstrate that TAF4b is both a direct and indirect regulator of cell cycle-related gene expression programs during ProSpg quiescence. By comparing the transcriptome changes in male and female Taf4b-deficient embryonic germ cells, we revealed that TAF4b promotes sex-independent and -dependent gene expression pathways, highlighting its unique and critical role in the fertility of both sexes.

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