This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.6828808v1 18/3/477    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Sinha, S. Articles by Segal, E. PubMed PubMed Citation Articles by Sinha, S. Articles by Segal, E. Social Bookmarking                   What's this?

Methods

Systematic functional characterization of cis-regulatory motifs in human core promoters

¹ Department of Computer Science, University of Illinois Urbana-Champaign, Urbana, Illinois 61801, USA; ² Program in Epithelial Biology, Stanford University, Stanford, California 94305, USA; ³ Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel

A large number of cis-regulatory motifs involved in transcriptional control have been identified, but the regulatory context and biological processes in which many of them function are unknown. Here, we computationally identify the sets of human core promoters targeted by motifs, and systematically characterize their function by using a robust gene-set-based approach and diverse sources of biological data. We find that the target sets of most motifs contain both genes with similar function and genes that are coregulated in vivo, thereby suggesting both the biological process regulated by the motifs and the conditions in which this regulation may occur. Our analysis also identifies many motifs whose target sets are predicted to be regulated by a common microRNA, suggesting a connection between transcriptional and post-transcriptional control processes. Finally, we predict novel roles for uncharacterized motifs in the regulation of specific biological processes and certain types of human cancer, and experimentally validate four such predictions, suggesting regulatory roles for four uncharacterized motifs in cell cycle progression. Our analysis thus provides a concrete framework for uncovering the biological function of cis-regulatory motifs genome wide.

E-mail eran{at}weizmann.ac.il; fax +972-8-934-4122.

E-mail howchang{at}stanford.edu; fax (650) 723-8762.

⁴ These authors contributed equally to this work.

[Supplemental material is available online at www.genome.org.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6828808

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?