TAF4b transcription networks regulating early oocyte differentiation
Authors listMegan A Gura Soňa Relovská Kimberly M Abt Kimberly A Seymour Tong Wu Haskan Kaya James Turner Thomas G Fazzio Richard N Freiman
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.
Pages Epub ahead of print