Requirement of Tissue-Selective TBP-Associated Factor TAF _II 105 in Ovarian Development

Abstract

Transcription factor TFIID, composed of TBP and TAFII subunits, is a central component of the RNA polymerase II machinery. Here, we report that the tissue-selective TAFII105 subunit of TFIID is essential for proper development and function of the mouse ovary. Female mice lacking TAFII105 are viable but infertile because of a defect in folliculogenesis correlating with restricted expression of TAFII105 in the granulosa cells of the ovarian follicle. Gene expression profiling has uncovered a defective inhibin-activin signaling pathway in TAFII105-deficient ovaries. Together, these studies suggest that TAFII105 mediates the transcription of a subset of genes required for proper folliculogenesis in the ovary and establishes TAFII105 as a cell type-specific component of the mammalian transcriptional machinery.

TRF2: TRansForming the view of general transcription factors

“…23,25,[28][29][30][31] Several tissue-specific variants of TAFs have been discovered: TAF4 variants are important for ovarian development and spermatogenesis in mice, while Drosophila and human TAF5 and TAF7 paralogs are implicated in male gametogenesis, thus providing the TFIID with unique functions in a tissue-specific transcription environment. [32][33][34][35][36][37] Following the binding of TFIID, TFIIA binds and stabilizes the association of TFIID with the TATA-box. The formation of the TFIID-TFIIA-DNA complex is followed by the sequential binding of TFIIB, RNAP II/TFIIF, TFIIE and TFIIH, resulting in the assembly of the PIC.…”

Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID

“…TAF4b is similar in structure to its broadly expressed paralog TAF4 (TAF II 130). While TAF4 and TAF4b display overlapping expression patterns in certain cell types, TAF4b is essential for regulating the selective expression of ovarian-specific gene expression patterns required for female fertility (Freiman et al 2001).Several other members of the basal transcription machinery also exhibit cell-specific expression and regulation of genes in the testis. The Drosophila testes contain several unique isoforms of TAFs that are essential for fertility (Hiller et al 2004).…”

“…TAF4b is similar in structure to its broadly expressed paralog TAF4 (TAF II 130). While TAF4 and TAF4b display overlapping expression patterns in certain cell types, TAF4b is essential for regulating the selective expression of ovarian-specific gene expression patterns required for female fertility (Freiman et al 2001).…”

“…While most TFIID subunits are expressed and function broadly in most cell types, there are selective TFIID subunits that apparently have evolved to function in the specification of gonadal-specific programs of gene expression. In the mouse, TAF4b is a component of TFIID that is highly enriched in gonadal tissues and is required for ovarian follicle development (Freiman et al 2001). TAF4b is similar in structure to its broadly expressed paralog TAF4 (TAF II 130).…”

Human male infertility and its genetic causes

“…TAF4B , also called “ TAFII105 ” (RNA polymerase II, TATA box‐binding protein‐associated factor), has 15 exons and encodes an 862‐amino acid protein. It was found to have a predominant expression in the testis but very weak expression in the other organs and the authors found that the protein was enriched in mouse gonadal tissues 64. It was demonstrated that Taf4b ‐null young mice initially were fertile but became infertile by 3 months, with impaired gonocyte proliferation and a reduced expression of spermatogonial stem cell markers, indicating that the gene protein is required for normal spermatogenic maintenance in adults 65.…”