CREME: Cis-Regulatory Module Explorer for the human genome
International Computer Science Institute, 1947 Center Street, Berkeley, CA 94704, USA, 1 Department of Biochemistry, B400 Beckman Center, Stanford University, CA 94305, USA and 2 EEBI and Genome Biology Divisions, L-441 Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA
* To whom correspondence should be addressed. Tel: +1 510 6662988; Fax: +1 510 6662956; Email: roded{at}icsi.berkeley.edu
Correspondence may also be addressed to Ivan Ovcharenko. Tel: +1 925 4225035; Fax: +1 925 4222099; Email: ovcharenko1{at}llnl.gov
Received February 12, 2004; Revised and Accepted March 21, 2004
The binding of transcription factors to specific regulatory sequence elements is a primary mechanism for controlling gene transcription. Eukaryotic genes are often regulated by several transcription factors whose binding sites are tightly clustered and form cis-regulatory modules. In this paper, we present a web server, CREME, for identifying and visualizing cis-regulatory modules in the promoter regions of a given set of potentially co-regulated genes. CREME relies on a database of putative transcription factor binding sites that have been annotated across the human genome using a library of position weight matrices and evolutionary conservation with the mouse and rat genomes. A search algorithm is applied to this data set to identify combinations of transcription factors whose binding sites tend to co-occur in close proximity in the promoter regions of the input gene set. The identified cis-regulatory modules are statistically scored and significant combinations are reported and graphically visualized. Our web server is available at http://creme.dcode.org.
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