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J. Biol. Chem., Vol. 280, Issue 27, 25590-25595, July 8, 2005
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From the aDepartment of Molecular Biology and Biotechnology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan, bCore Research for Evolutional Science and Technology, Japan Science and Technology Agency, 4-1-8, Saitama 332-0012, Japan, cRIKEN Plant Science Center, 1-7-22, Kanagawa 230-0045, Japan, eInstitute for Botany, University of Hannover, Herrenhäuserstrasse 2, D-30419 Hannover, Germany,f Phenomenome Discoveries Inc., 204-407 Downey Road, Saskatoon, Saskatchewan S7N 4L8, Canada, gDepartment of Bioinformatics and Genomics, Graduate School of Information Science, Nara Institute of Science and Technology, 8916-5, Nara 630-0101, Japan,h Ehime Women's College, Baba 421, Ehime 798-0025, Japan, iKazusa DNA Research Institute, 2-6-7, Chiba 292-0818, Japan, and jMax-Planck-Institute for Chemical Ecology, Hans-Knöll-Strasse 8, D-07745 Jena, Germany
Since the completion of genome sequences of model organisms, functional identification of unknown genes has become a principal challenge in biology. Post-genomics sciences such as transcriptomics, proteomics, and metabolomics are expected to discover gene functions. This report outlines the elucidation of gene-to-gene and metabolite-to-gene networks via integration of metabolomics with transcriptomics and presents a strategy for the identification of novel gene functions. Metabolomics and transcriptomics data of Arabidopsis grown under sulfur deficiency were combined and analyzed by batch-learning self-organizing mapping. A group of metabolites/genes regulated by the same mechanism clustered together. The metabolism of glucosinolates was shown to be coordinately regulated. Three uncharacterized putative sulfotransferase genes clustering together with known glucosinolate biosynthesis genes were candidates for involvement in biosynthesis. In vitro enzymatic assays of the recombinant gene products confirmed their functions as desulfoglucosinolate sulfotransferases. Several genes involved in sulfur assimilation clustered with O-acetylserine, which is considered a positive regulator of these genes. The genes involved in anthocyanin biosynthesis clustered with the gene encoding a transcriptional factor that up-regulates specifically anthocyanin biosynthesis genes. These results suggested that regulatory metabolites and transcriptional factor genes can be identified by this approach, based on the assumption that they cluster with the downstream genes they regulate. This strategy is applicable not only to plant but also to other organisms for functional elucidation of unknown genes.
Received for publication, March 2, 2005 , and in revised form, May 2, 2005.
* This work was supported in part by Core Research for Evolutional Science and Technology of Japan Science and Technology Agency, by grants-in-aid from the Ministry of Education, Science, Culture, Sports, and Technology, Japan, and by the project "Development of Fundamental Technologies for Controlling the Process of Material Production of Plants" from New Energy and Industrial Technology Development Organization. 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 a supplemental figure.
d Both authors contributed equally to this work.
k To whom correspondence should be addressed. Tel.: 81-43-290-2904; Fax: 81-43-290-2905; E-mail: ksaito{at}faculty.chiba-u.jp.
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