TAF4b transcription networks regulating early oocyte differentiation.

Megan A Gura, Soňa Relovská, Kimberly M Abt, Kimberly A Seymour, Tong Wu, Haskan Kaya, James M A Turner, Thomas G Fazzio, Richard N Freiman

Development (Cambridge, England) 2022 Feb 01

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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. © 2022. Published by The Company of Biologists Ltd.

Citation

Megan A Gura, Soňa Relovská, Kimberly M Abt, Kimberly A Seymour, Tong Wu, Haskan Kaya, James M A Turner, Thomas G Fazzio, Richard N Freiman. TAF4b transcription networks regulating early oocyte differentiation. Development (Cambridge, England). 2022 Feb 01;149(3)