Project description:Research has shown that Taf4b-deficient female mice display excessive perinatal germ cell death, delayed germ cell cyst breakdown, and increased chromosome asynapsis. Therefore, we hypothesized that TAF4b, as part of TFIID, regulates oogenesis and meiotic gene programs. However, the transcriptomic effects of Taf4b-deficiency and how this may lead to the infertility we observe in mice has not yet been studied. Therefore, we performed RNA-seq to examine gene expression changes in E16.5 female Taf4b-heterozygous and Taf4b-deficient germ cells
Project description:Research has shown that Taf4b-deficient female mice display excessive perinatal germ cell death, delayed germ cell cyst breakdown, and increased chromosome asynapsis. Therefore, we hypothesized that TAF4b, as part of TFIID, regulates oogenesis and meiotic gene programs. However, the transcriptomic effects of Taf4b-deficiency and how this may lead to the infertility we observe in mice has not yet been studied. Therefore, we performed RNA-seq to examine gene expression changes in E14.5 female Taf4b-wildtype, Taf4b-heterozygous, and Taf4b-deficient germ cells
Project description:Taf4b-deficient male mice are initially sub-fertile and become infertile due to a depletion of the spermatogonial stem cell (SSC) reserve. During embryonic time points, significantly reduced numbers of germ cells have been observed in the Taf4b-deficient male gonad and previous research has shown that Taf4b mRNA expression peaks at E15.5. Therefore, we hypothesized that TAF4b, as part of TFIID, regulates cell cycle and SSC gene programs. We performed RNA-seq to examine gene expression changes in E14.5 and E16.5 male Taf4b-wildtype, Taf4b-heterozygous, and Taf4b-deficient germ cells
Project description: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 modification/organization, and X-linked genes. Furthermore, dysregulated genes in Taf4b-deficient oocytes exhibit an unexpected amount of overlap with dysregulated genes in oocytes from XO female mice, a mouse model of Turner Syndrome. 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 alternative mode of promoter interaction. Together, our data connect several gene regulatory nodes that contribute to the precise development of the mammalian ovarian reserve.
Project description: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.
