EXPLORING PROKARYOTIC ONE-COMPONENT TRANSCRIPTION FACTORS

EXPLORING PROKARYOTIC

ONE-COMPONENT TRANSCRIPTION FACTORS

DEVELOPING GENERALLY APPLICABLE TOOLS TO INVESTIGATE

TETR FAMILY TRANSCRIPTIONAL REGULATORS

By SANG KYUN AHN, B.Sc.

McMaster University

A Thesis Submitted to the School of Graduate Studies in Partial Fulfilment

of the Requirements for the Degree Doctor of Philosophy

McMaster University ? Copyright by Sang Kyun Ahn, December 2012

DOCTOR OF PHILOSOPHY (2012)

(Biochemistry and Biomedical Sciences)

McMaster University

Hamilton, Ontario

TITLE: Development of Generally Applicable Tools to Investigate TetR Family

Transcriptional Regulators

AUTHOR: Sang Kyun Ahn, B.Sc. (McMaster University)

SUPERVISOR: Professor J.R. Nodwell

NUMBER OF PAGES: xv, 179

ii

ABSTRACT

Bacteria adapt to changes in their environment by regulating gene transcription.

TetR family transcriptional regulators (TFRs) constitute one of the largest groups

of bacterial transcription factors and thus, characterization of TFRs is anticipated

to be crucial for a better understanding of prokaryotic physiology. Of significant

importance, the majority of TFRs are predicted to respond to small-molecule

signals and an emerging paradigm suggests that identifying ligands of TFRs can

provide direct insight into the biochemical functions of the genes they regulate.

Regulatory target genes and small-molecule ligands are unknown for all but a

few TFRs and therefore, generally applicable tools for identifying these basic

elements of TFRs are highly desirable. We first investigated the use of genome

context as a predictive tool for identifying regulatory targets of TFRs. We find that

the majority of TFRs are divergently oriented from a neighboring gene, and those

with a ................
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