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Originally published In Press as doi:10.1074/jbc.M203487200 on April 12, 2002

J. Biol. Chem., Vol. 277, Issue 29, 26652-26661, July 19, 2002
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Genome-wide Profiling of Promoter Recognition by the Two-component Response Regulator CpxR-P in Escherichia coli*

Peter De WulfDagger §||, Abigail M. McGuire**Dagger Dagger , Xueqiao LiuDagger , and Edmund C. C. LinDagger §§

From the Dagger  Department of Microbiology and Molecular Genetics and ** Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115

In Escherichia coli, the two-component Cpx system comprising the CpxA sensor kinase and the CpxR response regulator modulates gene expression in response to a variety of stresses including membrane-protein damage, starvation, and high osmolarity. To date, the few known CpxR-P target operons were mostly identified by genetic screens. To facilitate the discovery of all target operons, we derived a 15-bp weighted matrix for CpxR-P recognition that takes into account the relative base frequency at each nucleotide position. This matrix essentially consists of two tandem 5'-GTAAA-3' motifs separated by a 5-bp linker. All of the 15-bp stretches on both strands of the E. coli MG1655 genome were then scored for their degree of matching with the matrix and classified in statistical deviation groups. The effectiveness of this screening is indicated by the identification of eight new target operons (ung, ompC, psd, mviA, aroK, rpoErseABC, secA, and aer) among eleven candidates tested. Moreover, the matrix score correlates with the likelihood that a site is a true target and with the relative site affinity for CpxR-P in vitro. Our data indicate that some 100 operons are under direct CpxR-P control and that the signal transduction pathway interacts with several other control circuits in manners hitherto unanticipated.


* This work was supported by Public Health Service Grant GM40993 from the National Institute of General Medical Sciences, National Institutes of Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Present address: Dept. of Biology, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139.

Both authors contributed equally to this work.

|| Former Postdoctoral D. Collen Fellow of the Belgian American Educational Foundation.

Dagger Dagger Former predoctoral fellow of the Howard Hughes Medical Institute.

§§ To whom correspondence should be addressed: Dept. of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, MA 02115. Tel.: 617-432-1925; Fax: 617-738-7664; E-mail: elin@hms.harvard.edu.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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