Dynamic and regulated TAF gene expression during mouse embryonic germ cell development

Germ cells undergo many developmental transitions before ultimately becoming either eggs or sperm, and during embryonic development these transitions include epigenetic reprogramming, quiescence, and meiosis. To begin understanding the transcriptional regulation underlying these complex processes, we examined the spatial and temporal expression of TAF4b, a variant TFIID subunit required for fertility, during embryonic germ cell development. By analyzing published datasets and using our own experimental system to validate these expression studies, we determined that both Taf4b mRNA and protein are highly germ cell-enriched and that Taf4b mRNA levels dramatically increase from embryonic day 12.5-18.5. Surprisingly, additional mRNAs encoding other TFIID subunits are coordinately upregulated through this time course, including Taf7l and Taf9b. The expression of several of these germ cell-enriched TFIID genes is dependent upon Dazl and/or Stra8, known regulators of germ cell development and meiosis. Together, these data suggest that germ cells employ a highly specialized and dynamic form of TFIID to drive the transcriptional programs that underlie mammalian germ cell development. Author summary Assisted reproductive therapy and fertility preservation are increasingly used to improve human reproduction across the world, yet there are still many unanswered questions regarding what factors govern the development of eggs and sperm and how these factors work together. We previously identified a subunit of the general transcription factor TFIID, TAF4b, that is essential for fertility. However, many basic characteristics of how Taf4b and its associated TFIID family members contribute to the formation of healthy sperm and eggs in mice and humans remain unknown. In this study, we find that mouse Taf4b and several closely related TFIID subunits become highly abundant during mouse embryonic gonad development, specifically in the cells that ultimately become eggs and sperm. Here, we analyzed data from public repositories and isolated these developing cells to examine their gene expression patterns throughout embryonic development. Together these data suggest that the dynamic expression of Taf4b and other TFIID family members are dependent on the well-established reproductive cell regulators Dazl and Stra8. This understanding of Taf4b gene expression and regulation in mouse reproductive cell development is likely conserved during development of human cells and offers novel insights into the interconnectedness of the factors that govern the formation of healthy eggs and sperm.