Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex

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Publication Type dissertation
School or College School of Medicine
Department Biochemistry
Author Close, Devin W
Title Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex
Date 2010-02-19
Description Proper gene expression relies on the precise coordination of cellular processes that influence packaging, transcription, and processing of the genetic material. Linkage and regulation of these processes is organized by factors that remodel and modify nucleosomes, regulate transcription, and influence RNA processing and export. One of these factors, Spt6, is a large (~168kDa), essential, highly conserved, and functionally diverse eukaryotic protein. Best known as a histone chaperone capable of altering the structure of nucleosomes, Spt6 has also been shown to function as a transcription elongation factor as well as a critical component for proper RNA processing. Although a broader role for Spt6 is reasonably well-understood, very little is known about the functional and mechanistic details of this multifaceted protein. Beyond studying Spt6 directly, insight into Spt6 function may come from complimentary studies on the bacterial protein Tex. Tex is a transcription elongation factor predicted to be a structurally similar to Spt6. The function of Tex is not well-understood, but may be functioning in a homologous manner to Spt6 in two vastly different transcriptional environments. In order to gain insight into the mechanism of Spt6 and Tex, the work presented in this thesis has focused on structural and biochemical studies of Spt6 from Saccharomyces cerevisiae and the related Tex protein from Pseudomonas aeruginosa. To this end, several Spt6 crystal structures have been determined resulting in a nearly complete composite model for Spt6. Along with a series of domains predicted to mediate protein and nucleic acid interactions, the structure reveals a novel tandem SH2 domain consisting of the only two SH2 folds known in yeast. Biochemical analysis of Spt6 demonstrates its capacity to interact with an array of functionally relevant protein and nucleic acid substrates which provide clues into mechanisms underlying the various functions of Spt6. Parallel studies on Tex demonstrate a strikingly similar structure and domain architecture to that of the Spt6 core. Structural and biochemical work described in this thesis lays the foundation for further in vitro and in vivo studies aimed at a better understanding of how Spt6 and Tex regulate gene expression. The highly similar core structure shared between Spt6 and Tex may ultimately prove to be a protein scaffold for regulating transcription in both eukaryotic and prokaryotic organisms.
Type Text
Publisher University of Utah
Subject Transcription Factors
Subject MESH Transcriptional Elongation Factors; Histone Chaperones; Nucleosome Assembly Protein 1
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Structural and biochemical studies of the transcription elongation factors spt6 and tex." Spencer S. Eccles Health Sciences Library. Print version of " structural and biochemical studies of the transcription elongation factors spt6 and tex." available at J. Willard Marriott Library. QP6.5 2009.C56.
Rights Management © Devin W. Close
Format Medium application/pdf
Format Extent 4,073,576 bytes
Source Original: University of Utah Spencer S. Eccles Health Sciences Library
Conversion Specifications Original scanned on Fujitsu fi-5220G as 400 dpi to pdf using ABBYY FineReader 10
ARK ark:/87278/s6zg76r1
Setname ir_etd
Date Created 2012-04-23
Date Modified 2021-05-06
ID 192773
Reference URL