TBP2 is essential for germ cell development by regulating transcription and chromatin condensation in the oocyte

Abstract

Development of the germline requires consecutive differentiation events. Regulation of these has been associated with germ cell-specific and pluripotency-associated transcription factors, but the role of general transcription factors (GTFs) remains elusive. TATA-binding protein (TBP) is a GTF involved in transcription by all RNA polymerases. During ovarian folliculogenesis in mice the vertebrate-specific member of the TBP family, TBP2/ TRF3, is expressed exclusively in oocytes. To determine TBP2 function in vivo, we generated TBP2-deficient mice. We found that Tbp2 À/À mice are viable with no apparent phenotype. However, females lacking TBP2 are sterile due to defective folliculogenesis, altered chromatin organization, and transcriptional misregulation of key oocyte-specific genes. TBP2 binds to promoters of misregulated genes, suggesting that TBP2 directly regulates their expression. In contrast, TBP ablation in the female germline results in normal ovulation and fertilization, indicating that in these cells TBP is dispensable. We demonstrate that TBP2 is essential for the differentiation of female germ cells, and show the mutually exclusive functions of these key core promoter-binding factors, TBP and TBP2, in the mouse.[Keywords: TBPL2; TRF3; TBP; Zp3; RNA Polymerase II; ovary] Supplemental material is available at http://www.genesdev.org.

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

“…51,52 A similar phenotype with failure to undergo the secondary follicle-to-antral follicle transition during folliculogenesis is observed in females that lack Taf4b (a germ cell-specific subunit of TFIID), 53 Yy1, 54 or Tbp2 (TATA-binding protein 2). 55 In particular, female mice deficient in the oocyte-specific TBP2 display phenotypes very similar to that observed for Hdac1:2 −/− mice, including infertility, small ovaries, arrest of follicle growth before antrum formation, a decrease in Pol II CTD S2 phosphorylation and histone H3K4 methylation. 55 The similarity in phenotypes suggests that Hdac1 and Hdac2 double mutants and these transcriptional factor mutants share a common mechanism that is linked to a decrease in transcription.…”

“…55 In particular, female mice deficient in the oocyte-specific TBP2 display phenotypes very similar to that observed for Hdac1:2 −/− mice, including infertility, small ovaries, arrest of follicle growth before antrum formation, a decrease in Pol II CTD S2 phosphorylation and histone H3K4 methylation. 55 The similarity in phenotypes suggests that Hdac1 and Hdac2 double mutants and these transcriptional factor mutants share a common mechanism that is linked to a decrease in transcription. Indeed, a detailed analysis using mice lacking different combinations of Hdac1 and Hdac2 suggests a threshold level of transcription is required for oocyte development ( Figure 3).…”

Molecular cytogenetic characterization of two Turner syndrome patients with mosaic ring X chromosome

“…As case 1 had a smaller r (X) chromosome compared to case 2, we analysed the additional genes deleted and found that the extra region deleted in case 1 (Xq21.33-Xq22.1) were harbouring genes involved in thyroid hormone signalling, insulin receptor signalling, meiosis regulation, cell cycle regulation and chromatin organization. Alterations in these pathways are reported to be responsible for ovarian dysfunction [1,5,9,31,36,46].…”

TRF2: TRansForming the view of general transcription factors

“…53,56 TRF3 has also been shown to form a complex with TAF3 and play a role in the ex-vivo differentiation of mouse myoblast to myotubes. 57,58 As skeletal muscle differentiation is unaffected in TRF3 knockout mice, 59 the involvement of TRF3 in terminal differentiation in different species awaits further investigation. Importantly, TRF3 of Xenopus and zebrafish is mainly expressed in oocytes and is essential for embryogenesis.…”

“…52,54 Mouse TRF3, which is exclusively expressed in oocytes, is essential for the differentiation of female germ cells but not for embryonic development. 59 TRF2 is the TRF protein with the least similarity to TBP. [60][61][62][63][64][65] In 1999-2000, when different research groups have cloned TRF2 from multiple species, different names were coined.…”