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Microbiology and Molecular Biology Reviews, September 2009, p. 481-509, Vol. 73, No. 3
1092-2172/09/$08.00+0     doi:10.1128/MMBR.00037-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Mechanisms and Evolution of Control Logic in Prokaryotic Transcriptional Regulation

Sacha A. F. T. van Hijum,1,2,{dagger}* Marnix H. Medema,1,{dagger},{ddagger} and Oscar P. Kuipers1,3*

Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands,1 Interfacultary Centre of Functional Genomics, Ernst Moritz Arndt Universität, Greifswald, Germany,2 Kluyver Centre for Genomics of Industrial Fermentation, Delft, The Netherlands3

Summary: A major part of organismal complexity and versatility of prokaryotes resides in their ability to fine-tune gene expression to adequately respond to internal and external stimuli. Evolution has been very innovative in creating intricate mechanisms by which different regulatory signals operate and interact at promoters to drive gene expression. The regulation of target gene expression by transcription factors (TFs) is governed by control logic brought about by the interaction of regulators with TF binding sites (TFBSs) in cis-regulatory regions. A factor that in large part determines the strength of the response of a target to a given TF is motif stringency, the extent to which the TFBS fits the optimal TFBS sequence for a given TF. Advances in high-throughput technologies and computational genomics allow reconstruction of transcriptional regulatory networks in silico. To optimize the prediction of transcriptional regulatory networks, i.e., to separate direct regulation from indirect regulation, a thorough understanding of the control logic underlying the regulation of gene expression is required. This review summarizes the state of the art of the elements that determine the functionality of TFBSs by focusing on the molecular biological mechanisms and evolutionary origins of cis-regulatory regions.

* Corresponding author. Present address for S. A. F. T. van Hijum: NIZO Food Research, P.O. Box 20, 6710 BA Ede, The Netherlands. Phone: 0031-318-659511. Fax: 0031-318-650400. E-mail: sacha.vanhijum{at}nizo.nl. Mailing address for O. P. Kuipers: Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands. Phone: 0031-50-3632093. Fax: 0031-50-3632348. E-mail: o.p.kuipers{at}rug.nl

{dagger} S.A.F.T.V.H. and M.H.M. contributed equally.

{ddagger} Present address: Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Kerklaan 30, 9751 NN Haren, The Netherlands.

Microbiology and Molecular Biology Reviews, September 2009, p. 481-509, Vol. 73, No. 3
1092-2172/09/$08.00+0     doi:10.1128/MMBR.00037-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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