Bioinformatics Vol. 19 Suppl. 1 2003
Pages i283-i291
© 2003 Oxford University Press
CREME: a framework for identifying cis-regulatory modules in human-mouse conserved segments
1 International Computer Science Institute, 1947
Center St., Suite 600, Berkeley CA-94704
2 Genome Sciences Department, Lawrence Berkeley
National Laboratory, Berkeley CA-94720
3 Department of Biochemistry, B400 Beckman Center,
Stanford University CA-94305, USA
Received on January 6, 2003
; accepted on February 20, 2003
Motivation: The binding of transcription factors to specific regulatory sequence elements is a primary mechanism for controlling gene transcription. Recent findings suggest a modular organization of binding sites for transcription factors that cooperate in the regulation of genes. In this work we establish a framework for finding recurrent cis-regulatory modules in the promoters of a selected set of genes and scoring their statistical significance.
Results: Proceeding from a database of identified binding site motifs and their genomic locations we seek motifs whose frequency in the selected promoters is different than in a background promoter set. We present several statistical tests designed for this purpose. We provide a hashing algorithm for detecting combinations of these motifs that co-occur in clusters within the selected promoters. The significance of such co-occurrences is evaluated using novel statistical scores. Our methods are combined in CREME, a suite of software which includes a browser for viewing the pattern of occurrence of selected cis-regulatory modules. We applied our methodology to find modules within human-mouse conserved promoter segments, focusing on cell cycle regulated genes and stress response related genes. To validate the biological significance of the identified modules we tested whether the associated genes tended to be co-expressed or share similar function. In the cell cycle set five of the seven identified sets of genes were coherently expressed. On the stress response data four of the six detected sets fell predominantly into well-defined functional sub-categories.
Availability: http://icsi.berkeley.edu/~roded/creme.html
Contact: roded{at}icsi.berkeley.edu.
Keywords: Cis-regulatory module, transcription factor binding site, motif cluster, statistical test.
* To whom correspondence should be addressed.
These authors contributed equally
to this work.
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