BMC Genomics Research article The DtxR protein acting as dual transcriptional regulator directs a global regulatory network involved in iron metabolism of Corynebacterium glutamicum Iris Brune1,2, Hendrikje Werner1,2, Andrea T Hüser1, Jörn Kalinowski1, Alfred Pühler2 and Andreas Tauch*1 BioMed Central Open Access Address: 1Institut für Genomforschung, Centrum für Biotechnologie, Universität Bielefeld, Universitätsstraße 25, D-33615 Bielefeld, Germany and 2Lehrstuhl für Genetik, Fakultät für Biologie, Universität Bielefeld, Universitätsstraße 25, D-33615 Bielefeld, Germany Email: Iris Brune - Iris.Brune@Genetik.Uni-Bielefeld.DE; Hendrikje Werner - Hendrikje.Werner@Genetik.Uni-Bielefeld.DE; Andrea T Hüser - Andrea.Hueser@Genetik.Uni-Bielefeld.DE; Jörn Kalinowski - Joern.Kalinowski@Genetik.Uni-Bielefeld.DE; Alfred Pühler - puehler@Genetik.Uni-Bielefeld.DE; Andreas Tauch* - Andreas.Tauch@Genetik.Uni-Bielefeld.DE * Corresponding author Published: 09 February 2006 BMC Genomics 2006, 7:21 doi:10.1186/1471-2164-7-21 This article is available from: http://www.biomedcentral.com/1471-2164/7/21 Received: 09 December 2005 Accepted: 09 February 2006 © 2006 Brune et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: The knowledge about complete bacterial genome sequences opens the way to reconstruct the qualitative topology and global connectivity of transcriptional regulatory networks. Since iron is essential for a variety of cellular processes but also poses problems in biological systems due to its high toxicity, bacteria have evolved complex transcriptional regulatory networks to achieve an effective iron homeostasis. Here, we apply a combination of transcriptomics, bioinformatics, in vitro assays, and comparative genomics to decipher the regulatory network of the iron-dependent transcriptional regulator DtxR of Corynebacterium glutamicum. Results: A deletion of the dtxR gene of C. glutamicum ATCC 13032 led to the mutant strain C. glutamicum IB2103 that was able to grow in minimal medium only under low-iron conditions. By performing genome- wide DNA microarray hybridizations, differentially expressed genes involved in iron metabolism of C. glutamicum were detected in the dtxR mutant. Bioinformatics analysis of the genome sequence identified a common 19-bp motif within the upstream region of 31 genes, whose differential expression in C. glutamicum IB2103 was verified by real-time reverse transcription PCR. Binding of a His-tagged DtxR protein to oligonucleotides containing the 19-bp motifs was demonstrated in vitro by DNA band shift assays. At least 64 genes encoding a variety of physiological functions in iron transport and utilization, in central carbohydrate metabolism and in transcriptional regulation are controlled directly by the DtxR protein. A comparison with the bioinformatically predicted networks of C. efficiens, C. diphtheriae and C. jeikeium identified evolutionary conserved elements of the DtxR network. Conclusion: This work adds considerably to our currrent understanding of the transcriptional regulatory network of C. glutamicum genes that are controlled by DtxR. The DtxR protein has a major role in controlling the expression of genes involved in iron metabolism and exerts a dual regulatory function as repressor of genes participating in iron uptake and utilization and as activator of genes responsible for iron storage and DNA protection. The data suggest that the DtxR protein acts as global regulator by controlling the expression of other regulatory proteins that might take care of an iron-dependent regulation of a broader transcriptional network of C. glutamicum genes. Page 1 of 19 (page number not for citation purposes)