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J. Biol. Chem., Vol. 281, Issue 12, 8090-8099, March 24, 2006
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From the
Laboratorio de Microbiología y Genética Molecular, Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico and the Graduate School of Information Science/Human Informatics and CREST/JST, Nagoya University, Nagoya 464-8601, Japan
Cyclicdiguanylicacid(c-di-GMP;cGpGp)isaglobalsecondmessenger controlling motility and adhesion in bacterial cells. Intracellular concentrations of c-di-GMP depend on two opposite activities: diguanylate cyclase, recently assigned to the widespread GGDEF domain, and c-di-GMP-specific phosphodiesterase, associated with proteins harboring the EAL domain. To date, little is known about the targets of c-di-GMP in the cell or if it affects transcriptional regulation of certain genes. In order to expand our knowledge of the effect of this molecule on the bacterial metabolism, here we report on the Escherichia coli transcriptional profile under high levels of c-di-GMP. We show that an important number of genes encoding cell surface and membrane-bound proteins are altered in their transcriptional activity. On the other hand, genes encoding several transcriptional factors, such as Fur, RcsA, SoxS, and ZraR, are up-regulated, and others, such as GadE, GadX, GcvA, and MetR, are down-regulated. Transcription of motility and cell division genes were altered, and consistent with this was the physiological analysis of cells overexpressing yddV,adiguanylatecyclase;thesecellsdisplayedanabnormalcelldivision process when high levels of c-di-GMP were present. We also show evidence that the diguanylate cyclase gene yddV is co-transcribed with dos,a heme base oxygen sensor with c-di-GMP-specific phosphodiesterase activity. A 
dos::kan mutation rendered the cells unable to divide properly,suggestingthatdosandyddVmaybepartofafine-tuningmechanism for regulating the intracellular levels of c-di-GMP.
Received for publication, September 30, 2005 , and in revised form, January 4, 2006.
* This work was supported by Programa de Apoyo a Proyectos de Investigación e Innovación Technológica (PAPIIT) Universidad Nacional Autónoma de México (UNAM) Grants IN205200 and IN207703 and Consejo Nacional de Ciencia y Tecnologia (CONACYT) Mexico Grants J33369 and 42580. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains supplemental Tables I-IV.
1 Recipient of a Ph.D. studentship from CONACYT and Dirección General de Estudios de Posgrado (DGEP) Universidad Nacional Autónoma de México (UNAM).
2 To whom correspondence should be addressed: Laboratorio de Microbiología y Genética Molecular, Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, P. O. Box 70-228, Ciudad Universitaria, Mexico City 04510, México. Tel.: 52-55-56223840; Fax: 52-55-56223855; E-mail: jmh{at}biomedicas.unam.mx.
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