Abstract

Traditional transcription factor binding site analyses focus solely on the nucleotide composition of site despite the fact that more recent studies have shown transcription factors to rely on the DNA structural features within and surrounding their binding sites. In this study a metric of intrinsic DNA flexibility referred to as the TRX scale is used to assess the structural features within functionally annotated binding sites and their up- and downstream flanking regions based on their Shannon information content (IC). Two methods of sequence alignment, center and a novel delta TRX based multiple sequence alignment, are compared. The results show that at least 95% of all up- and downstream flanking regions contained more IC in their structural signature as defined by the TRX scale. Between 23% and 35% (excluding and including bridging phosphate bonds, respectively) of flanking regions also showed significant differences between the sets of confirmed and non-confirmed matches. However, few to no significant differences in IC were observed in consensus match regions where sequence dependent major groove contacts are most likely to occur. These findings support the notion that structural context is highly important in the distinction between true and false binding sites. Enhanced consensus logos are demonstrated for the visualization of these structural signatures. While delta TRX based multiple sequence alignment appeared to be superior in flanking regions when compared to center alignment, further analyses are needed in order to increase the confidence in these findings.

Library of Congress Subject Headings

DNA--Conformation; Saccharomyces cerevisiae--Genetics

Publication Date

5-19-2014

Document Type

Thesis

Student Type

Graduate

Degree Name

Bioinformatics (MS)

Department, Program, or Center

Thomas H. Gosnell School of Life Sciences (COS)

Advisor

Gregory A. Babbitt

Advisor/Committee Member

Feng Cui

Advisor/Committee Member

Gary R. Skuse

Comments

Physical copy available from RIT's Wallace Library at QP624 .S38 2014

Campus

RIT – Main Campus

Plan Codes

BIOINFO-MS

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