With the entire genome sequence of Bacillus subtilis now determined, one of the next major targets of B. subtilis genomics is to elucidate its complete gene regulatory network. To this end, the results of systematic experiments should be compared with the rich source of individual experimental results accumulated so far. We therefore constructed the DBTBS database, containing a collection of experimentally validated gene regulatory relations and the corresponding transcription factor binding sites upstream of B. subtilis genes. Its current version is constructed by surveying 873 references and contains the information of 116 binding factors and 1253 gene regulatory relations. For each promoter, all of its known cis-elements are listed according to their positions, while these cis-elements are aligned to illustrate the consensus sequence for each transcription factor. All probable transcription factors coded in the genome were classified using Pfam motifs. Multiple alignments of upstream sequences between B. halodurans, B. stearothermophilus, and B. subtilis are also shown.
Recent develoments :
The DBTBS database was recently reorganized to show operons instead of individual genes as the building blocks of gene regulatory networks. DBTBS now contains 463 experimentally known operons, as well as their terminator sequences if identifiable. In addition, 517 transcriptional terminators were identified computationally. (De Hoon, M.J.L. et al., PLoS Comput. Biol. 1, e25 (2005)).
We are grateful to Naotake Ogasawara for useful comments, and Takahiro Ishii, Ken-ichi Yoshida, Goro Terai, Mitsuteru Nakao and Yasutaro Fujita, who have contributed to earlier versions of this database. This work was partly supported by a Grant-in Aid for Scientific Research on Priority Areas Genome Information Science from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
1. Ishii, T. et al. (2001). Nucleic Acids Res. 29, 278-280.
2. Makita, Y. et al. (2004). Nucleic Acids Res. 32, D75-D77
SubtiList is the reference database dedicated to the genome of Bacillus subtilis 168, the paradigm of Gram-positive endospore-forming bacteria. Developed in the framework of the B. subtilis genome project (1), SubtiList provides a curated dataset of DNA and protein sequences, combined with the relevant annotations and functional assignments (2). Information about gene functions and products is continuously updated by linking relevant bibliographic references. Recently, sequence corrections arising from both systematic verifications and submissions by individual scientists were included in the reference genome sequence (3). SubtiList is based on a generic relational data schema and World-Wide Web interface developed for the handling of bacterial genomes, called GenoList. The WWW interface was designed to allow users to easily browse through genome data and retrieve information according to common biological queries. SubtiList also provides more elaborate tools, such as pattern searching, which are tightly connected to the overall browsing system. SubtiList is accessible at the URL http://genolist.pasteur.fr/SubtiList/. Similar bacterial databases are accessible at the URL http://genolist.pasteur.fr/.
Initial development stages (4) were performed in the framework of the European B. subtilis genome project (European Commission Biotechnology program — contracts BIO2-CT93-0272, BIO2-CT94-2011, BIO4-CT96-0655), coordinated by F. Kunst and supported by the BACillus Industrial Platform (BACIP). We thank the contribution at various stages of P. Glaser, A. Hénaut, C. Médigue, M. Pupin, and A. Viari. We acknowledge the fruitful collaboration with A. Bairoch and the SWISS-PROT team.
1. Kunst,F., Ogasawara,N., Moszer,I., Albertini,A.M., Alloni,G., Azevedo,V., Bertero,M.G., Bessières,P., Bolotin,A., Borchert,S., et al. (1997) The complete genome sequence of the Gram-positive bacterium Bacillus subtilis. Nature, 390,
2. Moszer,I. (1998) The complete genome of Bacillus subtilis: from sequence annotation to data management and analysis. FEBS Lett.,
3. Médigue,C., Rose,M., Viari,A. and Danchin,A. (1999) Detecting and analyzing DNA sequencing errors: toward a higher quality of the Bacillus subtilis genome sequence. Genome Res., 9, 1116-1127.
4. Moszer,I., Glaser,P. and Danchin,A. (1995) SubtiList: a relational database for the Bacillus subtilis genome. Microbiology, 141,
CSDBase (http://www.chemie.uni-marburg.de/~csdbase/) is an interactive Internet-embedded research platform providing detailed information on cold shock domain-containing proteins and bacterial cold shock responses. In its second release, access to CSDBase is completely independent of a specific computer system and/or browser and care has been taken to fully preserve the outfit and user interfaces of the initial version to provide convenient usage. In addition to the updated literature references, protein information and CSD-containing protein structure model content present in CSDBase, we have integrated a new database subcore harboring the entire results of the first DNA macroarray study of cold shocked Bacillus subtilis cells. These data can be searched and ranked according to multiple features such as gene name, gene expression at 37°C or 15°C, cold-induction factor, etc. and comprise all genes of the B. subtilis genome. On the basis of the flexible architecture of CSDBase we would like to invite researches from other work groups to integrate their data into this database after publication in order to (i) establish a central archive for world-wide accessible DNA array results of cold shocked bacteria, and (ii) overcome the usually reduced information content of array data publications that results from space limitations in scientific journals.
Recent develoments :
Since the initial release of CSDBase in January 2002 (Weber et al., 2002), many exciting new reports concerning nucleic acid binding proteins harboring the cold shock domain (CSD) have been published and were incorporated in the extended version of our current CSDBase literature retrieval subsystem. These reports describe the discovery of the first archaeal cold shock protein encoding DNA sequence (Beja et al., 2002) as well as the cloning, purification and biochemical characterization of the first eukaryotic cold shock protein Cla h 8 from Cladosporium herbarum (Falsone et al., 2002). Moreover, a number of previously determined bacterial cold shock protein structure coordinate files have now become available in the relevant protein structure databases (Delbruck et al., 2001, Kremer et al., 2001) and the first structure of a CSD from a Y-box protein has been solved (Kloks et al., 2002). Together with the previously available structural information on CSD-containing proteins, these extended data sets are currently used to re-calculate the complete CSD structure model collection that has been presented in the initial version of CSDBase (Weber et al., 2002). A newly performed sequence data acquisition has furthermore revealed that the number of known CSD-containing protein sequences has approximately doubled compared to what was known in January 2000. Also, according to these data it appears that CSD-containing proteins represent only a minor fraction of the plant glycine-rich protein family whose members predominantly possess the RBD/RRM motif(s). In addition to a regularly performed update of the CSDBase data content, the current release was designed to focus on two major improvements. These were (i) the conversion of CSDBase into a platform- and browser-independent environment to address a much broader scientific community, and (ii) the integration of a novel database subcore providing additional scientific data concerning bacterial cold shock responses. As a result, the new release of CSDBase does no longer require Microsoft Internet Explorer (version 5 or higher) as was the case with the previous version and now runs completely independent of a specific computer system and/or browser. Care has been taken to fully preserve the outfit and user interfaces of the initial release to provide convenient usage. Moreover, a new database subcore has been created that contains the entire DNA macroarray results from our recently published transcriptomic investigation of the cold shock response in Bacillus subtilis (Beckering et al., 2002). These data can be searched and ranked according to multiple features such as gene name, gene expression at 37°C or 15°C, cold-induction factor, etc. and comprise all genes of the B. subtilis genome. To initiate the establishment of a central location for the deposition of such world-wide accessible bacterial cold shock response-related DNA array data, we hereby invite researchers from other workgroups to contact us in order to integrate their data in a separate CSDBase database subcore of similar structure. Each database subcore can be password protected until the original data has been published elsewhere. We hope that this CSDBase-integrated database subsystem will allow to overcome the significantly reduced information content of array data publications that results from space limitations in scientific journals.
This work was supported by Sonderforschungsbereich 395 and Fonds der Chemischen Industrie.
Beckering, C.L., Steil, L., Weber, M.H.W., Völker, U., and Marahiel, M.A. (2002) Genomewide transcriptional analysis of the cold-shock response in Bacillus subtilis. J. Bacteriol. In press.
Beja, O., Koonin, E.V., Aravind, L., Taylor, L.T., Seitz, H., Stein, J.L., Bensen, D.C., Feldman, R.A., Swanson, R.V. and DeLong, E.F. (2002) Comparative genomic analysis of archaeal genotypic variants in a single population and in two different oceanic provinces. Appl Environ Microbiol, 68, 335-45.
Delbruck, H., Mueller, U., Perl, D., Schmid, F.X. and Heinemann, U. (2001) Crystal structures of mutant forms of the Bacillus caldolyticus cold shock protein differing in thermal stability. J Mol Biol, 313, 359-69.
Falsone, S.F., Weichel, M., Crameri, R., Breitenbach, M. and Kungl, A.J. (2002) Unfolding and double-stranded DNA binding of the cold shock protein homologue Cla h 8 from Cladosporium herbarum. J Biol Chem, 277, 16512-6.
Kloks, C.P., Spronk, C.A., Lasonder, E., Hoffmann, A., Vuister, G.W., Grzesiek, S. and Hilbers, C.W. (2002) The solution structure and DNA-binding properties of the cold-shock domain of the human Y-box protein YB-1. J Mol Biol, 316, 317-26.
Kremer, W., Schuler, B., Harrieder, S., Geyer, M., Gronwald, W., Welker, C., Jaenicke, R. and Kalbitzer, H.R. (2001) Solution NMR structure of the cold-shock protein from the hyperthermophilic bacterium Thermotoga maritima. Eur J Biochem, 268, 2527-39.
Weber, M.H., Fricke, I., Doll, N. and Marahiel, M.A. (2002) CSDBase: an interactive database for cold shock domain-containing proteins and the bacterial cold shock response. Nucleic Acids Res, 30, 375-8.