Coordinated regulation of gene expression by E ... - Jacobs University
Coordinated regulation of gene expression by E ... - Jacobs University
Coordinated regulation of gene expression by E ... - Jacobs University
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ABSTRACT<br />
Abstract<br />
Bacteria are omnipresent small organisms that posses impressive ability to adapt to their<br />
environment. Adaptation, a universal phenomenon seen at all different levels <strong>of</strong><br />
organizational complexity <strong>of</strong> life, is accomplished mainly <strong>by</strong> adjustment <strong>of</strong> the <strong>gene</strong><br />
<strong>expression</strong> pattern. Studies using microarray-mediated transcript pr<strong>of</strong>iling in E.coli<br />
demonstrated the existence <strong>of</strong> direct correlations between the global <strong>gene</strong> <strong>expression</strong><br />
patterns and different phases [Tao, 1999; Weber, 2005; Wei, 2001]. Previous work from<br />
our and other laboratories indicated that in E.coli the cellular transcription is under the<br />
control <strong>of</strong> a global regulatory network whose main components are - DNA<br />
topoisomerases, chromatin proteins modulating the supercoil dynamics <strong>of</strong> DNA and, the<br />
RNA polymerase. The aim <strong>of</strong> this project was to understand the basic structural<br />
mechanism <strong>of</strong> interaction <strong>of</strong> two <strong>of</strong> the components (DNA supercoiling and chromatin<br />
proteins) and the underlying functional coordination <strong>of</strong> <strong>gene</strong> <strong>expression</strong> in E.coli.<br />
To understand the coordination <strong>of</strong> the components, the problem was<br />
approached at two levels <strong>of</strong> complexity, (1) global – for this purpose we developed a<br />
novel DNA microarray-based approach combining mutations in the <strong>gene</strong>s <strong>of</strong> chromatin<br />
proteins with directional changes <strong>of</strong> DNA superhelicity and (2)local - at the level <strong>of</strong><br />
individual <strong>gene</strong> promoter, using as a model tyrT promoter system, to understand the<br />
molecular mechanism <strong>of</strong> the interplay between supercoiling and transcriptional<br />
regulators. The study has led us to propose that the global transcription <strong>regulation</strong> is<br />
spatiotemporally coordinated <strong>by</strong> the differential distribution <strong>of</strong> two types <strong>of</strong> information,<br />
‘analog’ and ‘digital’. The digital or discontinous property <strong>of</strong> an information is manifest<br />
in the pattern <strong>of</strong> expressed <strong>gene</strong>s at all times depending on the distribution <strong>of</strong> the analog<br />
component - DNA supercoiling - distribution <strong>of</strong> supercoiling in different parts <strong>of</strong> the<br />
genome. The analog component is continuously converted in the pattern <strong>of</strong> expressed<br />
<strong>gene</strong>s and vice versa, there<strong>by</strong> modulates the physiology to a dynamic equilibrium,<br />
which can be readjusted in response to changes in both the digital (mutation) and<br />
analog (growth phase or stress induced changes <strong>of</strong> supercoiling) information. On the<br />
example <strong>of</strong> tyrT promoter we demonstrate how the sequence organization <strong>of</strong> the