BMC Genomics Research article Identification of conserved domains in the promoter regions of nitric oxide synthase 2: implications for the species-specific transcription and evolutionary differences Daniel Rico1, Juan M Vaquerizas2, Hernán Dopazo2 and Lisardo Boscá*3 BioMed Central Open Access Address: 1Centro Nacional de Investigaciones Cardiovasculares, Melchor Fernández Almagro 3, 28029 Madrid, Spain, 2Bioinformatics Department, Centro de Investigación Príncipe Felipe, Autopista del Saler 16, 46013 Valencia, Spain and 3Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain Email: Daniel Rico - drico@cnio.es; Juan M Vaquerizas - jvaquerizas@cipf.es; Hernán Dopazo - hdopazo@cipf.es; Lisardo Boscá* - lbosca@iib.uam.es * Corresponding author Published: 8 August 2007 BMC Genomics 2007, 8:271 doi:10.1186/1471-2164-8-271 This article is available from: http://www.biomedcentral.com/1471-2164/8/271 Received: 3 October 2006 Accepted: 8 August 2007 © 2007 Rico 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 majority of the genes involved in the inflammatory response are highly conserved in mammals. These genes are not significantly expressed under normal conditions and are mainly regulated at the transcription and prost-transcriptional level. Transcription from the promoters of these genes is very dependent on NF-κB activation, which integrates the response to diverse extracellular stresses. However, in spite of the high conservation of the pattern of promoter regulation in κB-regulated genes, there is inter-species diversity in some genes. One example is nitric oxide synthase 2 (NOS-2), which exhibits a species-specific pattern of expression in response to infection or pro-inflammatory challenge. Results: We have conducted a comparative genomic analysis of NOS-2 with different bioinformatic approaches. This analysis shows that in the NOS-2 gene promoter the position and the evolutionary divergence of some conserved regions are different in rodents and non-rodent mammals, and in particular in primates. Two not previously described distal regions in rodents that are similar to the unique upstream region responsible of the NF-κB activation of NOS-2 in humans are fragmented and translocated to different locations in the rodent promoters. The rodent sequences moreover lack the functional κB sites and IFN-γ response sites present in the homologous human, rhesus monkey and chimpanzee regions. The absence of κB binding in these regions was confirmed by electrophoretic mobility shift assays. Conclusion: The data presented reveal divergence between rodents and other mammals in the location and functionality of conserved regions of the NOS-2 promoter containing NF-κB and IFN- γ response elements. Background The biological activity of most genes involved in adaptive responses is regulated mainly at the level of transcription, and to a lower extent at the post-transcriptional level [1]. A primary example is the highly conserved mammalian inflammatory response, which involves the coordinated transcriptional induction of multiple genes. In this proc- ess, an important integrating role is played by the tran- Page 1 of 10 (page number not for citation purposes)