Structural Studies of Spt6

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DESCRIPTION (provided by applicant): Regulation of gene expression is fundamental to cell function and viability. Disruption of gene expression is a universal feature of tumorigenesis. The enzyme responsible for expression of protein-encoding genes at the level of transcription, RNA polymerase II (RNAPII), is intricately controlled by a variety of essential factors. In addition, the chromatin status of a gene plays a critical role in its expression. Spt6 is a highly conserved and essential eukaryotic protein that functions both as a transcription elongation factor and as a regulator of chromatin structure. The aim of this research is to examine the molecular basis for Spt6 function in transcription and chromatin reorganization by determining crystal structures of Spt6 and relevant complexes. Direct interactions with Spt6 will be identified and characterized by biochemical analysis. Potential interactions with nucleosome structures will be pursued. Tex, a well conserved but poorly understood prokaryotic homolog of Spt6, will also be targeted for structural analysis. A particular focus is to characterize common features between Tex and Spt6, including interactions with the RNA processing exosome/degradosome complexes.