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

Maria M Mikedis,Richard N Freiman,Kimberly A Seymour,Megan A Gura,Dirk G De Rooij,David C Page

doi:10.1371/journal.pgen.1008515

Abstract

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.

Highlights

Healthy development and maintenance of germ cells is essential for the continuation of all sexually reproducing species
We previously identified a subunit of the general transcription factor TFIID, TAF4b, that is essential for fertility
Many basic characteristics of how TATA-binding protein (TBP)-Associated Factor 4b (Taf4b) and its associated TFIID family members contribute to the formation of healthy sperm and eggs in mice and humans remain unknown

Summary

Introduction

Healthy development and maintenance of germ cells is essential for the continuation of all sexually reproducing species. In the United States, approximately 10% of individuals face fertility issues, and worldwide, at least 1% of females experience primary ovarian insufficiency (POI), which is associated with infertility [1,2]. In most instances of POI and infertility, the underlying molecular causes are unknown [3]. Work from our laboratory has shown that a TBP-Associated Factor 4b (Taf4b)-deficient mouse model recapitulates many aspects of POI, including a premature depletion of the ovarian reserve and female infertility [4,5]. Since human studies implicate TAF4B as important for fertility and oocyte quality [7,8,9], our efforts to understand the molecular mechanisms underlying the expression and function of TAF4b in mouse germ cell development may contribute to our increased understanding of human fertility and infertility

Methods

Results

Discussion

Conclusion