Cell-type-selective expression of the TFIID subunit TAFII105 (renamed TAF4b) in the ovary is essential for proper follicle development. Although a multitude of signaling pathways required for folliculogenesis have been identified, downstream transcriptional integrators of these signals remain largely unknown. Here, we show that TAF4b controls the granulosa-cell-specific expression of the proto-oncogene c-jun, and together they regulate transcription of ovary-selective promoters. Instead of using cell-type-specific activators, our findings suggest that the coactivator TAF4b regulates the expression of tissue-specific genes, at least in part, through the cell-type-specific induction of c-jun, a ubiquitous activator. Importantly, the loss of TAF4b in ovarian granulosa cells disrupts cellular morphologies and interactions during follicle growth that likely contribute to the infertility observed in TAF4b-null female mice. These data highlight a mechanism for potentiating tissue-selective functions of the basal transcription machinery and reveal intricate networks of gene expression that orchestrate ovarian-specific functions and cell morphology.ovary ͉ TFIID ͉ short interfering RNA ͉ chromatin immunoprecipitation ͉ granulosa cells S pecific targeting of RNA polymerase (Pol) II to heteromorphic promoters dispersed throughout the genome and packaged into chromatin requires the function of a multitude of individual proteins and multiprotein complexes that collectively direct the modulation of RNA synthesis. At the core of this machinery are the general transcription factors that were first posited to be global in nature and not directly implicated in control of cell-type-specific gene expression. Rather, cell-typespecific expression patterns were largely attributed to DNAbinding activator and repressor proteins that were thought to be expressed in a highly cell-type-specific fashion (1). The general transcription factor IID (TFIID) is a large multiprotein transcription factor that lies at the core of the basal transcription machinery. TFIID is composed of the TATA-box-binding protein (TBP) and a common subset of TBP-associated factors (TAFs) that together perform promoter-selective and coactivator functions during transcription initiation (2). Together, genetic and biochemical studies suggest a conserved and formidable role of TFIID in the execution of global programs of gene expression.