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Genome-Wide Analysis of Transcriptional Regulation via TAF1 Kinase


Gene regulation is a complex mechanism and our knowledge of molecular pathways remains limited. In particular, current research examining transcriptional regulation emphasizes events that precede the initiation of transcription. However, correct regulation also requires turning off transcription when it’s no longer needed. Because DNA-bound activators interact with and recruit components of the basal transcription apparatus to the promoter, these basal factors could, in theory, mark the activators. Presumably, through post-translational modification after transcription, this process could lead to transcription termination. To determine this mechanism, previous studies have elucidated the relationship between the TATA-Binding Protein Associated Factor 1 (TAF1) and p53 in response to Ultra Violet (UV) DNA damage. The p53 tumor suppressor is a transcription factor that plays a critical role in guarding cell genomes against DNA damage. Among the genes induced by p53 is p21, which induces cell cycle arrest. TAF1 phosphorylates p53 at Thr55 on the p21 promoter, leading to p53 dissociation from the promoter and transcription termination. TAF1 is the largest subunit of general transcription factor TFIID and possesses intrinsic protein kinase activity. Because TAF1 is a component of general transcription machinery bound to many promoters, the following research was designed to elucidate how TAF1 contributes to transcriptional regulation via it’s DNA binding activities and kinase activities. This dissertation aims to reveal TAF1’s genome-wide response to UV induced DNA damage. My studies included an in-depth look into TAF1’s recruitment to the promoter via core promoter elements, novel TAF1 kinase targets, and the regulation of gene expression upon DNA damage via TAF1. These studies will provide important insights into how TAF1 impacts genome-wide transcription regulation and explores how to regulate transcription termination. Since the regulation of gene expression is a vital process for the integrity of organisms, this discovery provides an in-depth understanding of the cellular development of a wide range of species.

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