[Frontiers in Bioscience 8, d279-285, January 1, 2003]

TRANSCRIPTION FACTOR AS A TOPOLOGICAL HOMEOSTAT

Georgi Muskhelishvili 1 and Andrew Travers 2

1 Max Planck Institute for terrestrial Microbiology, Karl-von-Frisch Strasse, D-35043, Marburg, Germany; 2 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, England

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Effects of FIS binding on DNA structure
3.1. Global effect of FIS binding to supercoiled DNA
3.2. Local effect of FIS binding to promoter upstream regions
4. Regulation of promoter activity by FIS
4.1. Mechanistic relationship between the effects of FIS and supercoiling
4.2. Role of the DNA microloop
5. Mechanism of transcriptional activation by FIS
6. FIS as a topological optimiser
7. Acknowledgements
8. References

1. ABSTRACT

Abundant prokaryotic chromatin architectural proteins often function also as global transcriptional regulators. In addition, some of this class of proteins modulate the activity of cellular topoisomerases and hence, the superhelical density of DNA. The relationships between the global effect of these proteins on DNA topology and their local effects exerted on particular promoter regions remain largely unexplored. One of the best-characterised examples of this class of proteins is the pleiotropic regulator of metabolism FIS, which reduces the activity of DNA gyrase and counteracts the increase of the overall superhelicity of DNA during early exponential growth phase. Binding of FIS to supercoiled DNA molecules in vitro leads to theformation of branched structures and consequent multiplication of apical loops, whereas on bending the upstream regions of stable RNA promoters FIS acts as a topological homeostat maintaining high local levels of supercoiling required for promoter activity. We argue that the coordinated effects of FIS on the global and local DNA architecture optimise gene expression by channelling the free energy of negative supercoiling to specific, biologically relevant sites.