The Ovarian Requirement for Variant TFIID Subunit, TAF4b, in Mammalian Reproduction Lovasco, Lindsay A. creator 2009 xiii, 192 p. born digital Thesis (Ph.D.) -- Brown University (2010) Freiman, Richard director Atwood, Walter reader Gerbi, Susan reader Laney, Jeffrey reader Marr, Michael reader Brown University. Division of Biology and Medicine. Molecular Biology, Cell Biology, and Biochemistry sponsor theses TAF4b is a gonadal-encriched variant of the general transcription factor complex, TFIID. The studies presented here highlight the specific requirement for TAF4b in female mammalian fertility. Although TAF4b is differentially regulated in other tissues, there is no evidence to support its requirement outside of the gonad. Using a combination of in vivo and in vitro experimentation in the mouse and mammalian cell culture, we have shown that TAF4b directs both granulosa cell and oocyte-specific gene expression. Deletion of TAF4b leads to multiple ovarian deficiencies and accelerated depletion of follicle reserves, mimicking the human condition of Primary Ovarian Insufficiency. We have introduced a new set of putative TAF4b-target genes that are functionally significant to human reproduction and may underlie yet unidentified germline-specific processes. We have also identified a TAF4b-regulated germ cell-specific RNA helicase, Mov10l1, which may be involved in a novel mammalian RNAi pathway. Although preliminary studies have implicated TAF4b in extra-gondal proliferation, we have shown that it is not a general requirement for cell cycle progression in differentiated tissues. TAF4b does not appear necessary, despite consistently elevated expression, in proliferating cells. Similarly, TAF4b has been localized to a number of specific gene promoters, but we show here that TAF4b is not an absolute requirement for their normal expression in vivo. What we have observed during the characterization of this variant TAF may be residual activity carried through evolution, but not relevant to its essential function in the mammalian gonad. Mammalian OvariesTranscription RPB 20091218 engEnglish10.7301/Z0ST7N4SIn CopyrightCollection is open for research.dissertations