Transcriptional regulation is a fundamental biological process, and discovering, characterizing, and annotating transcriptional regulatory sequences is major post-genome-sequencing goal. We focus on two types of cis-regulatory sequences: promoters, which comprise the DNA sequence immediately surrounding a gene’s transcriptional start site, and cis-regulatory modules (CRMs)—in particular, positive regulatory sequences typically referred to as “enhancers”—which can lie tens of kilobases distant from their associated gene. We have curated the data on the majority of known CRMs in Drosophila and assembled them into the REDfly database. Using these data, we have obtained a number of new insights into the organizational principles of CRMs, and we are using these to develop new and improved methods for genome-wide computational CRM discovery. We have also undertaken a genome-wide survey of Drosophila promoters, with an emphasis on the promoters of neighboring genes and on alternative promoters of the same gene. We find that there is an unexpectedly high level of organization of promoter sequences throughout the genome. Together, our studies of promoters and CRMs will lead to increased understanding of genome organization, mechanisms of transcriptional regulation, and the interplay between these two important classes of cis-regulatory elements.

Kantorovitz, M.R., Kazemian, M., Robinson, G.E., Halfon, M.S. and Sinha, S. (2008). Supervised prediction of cis-regulatory modules in the Drosophila genome, without motif knowledge. Submitted.

Zhu, Q. and Halfon, M.S. (2008). Complex organizational structure of the genome revealed by genome-wide analysis of single and alternative promoters in Drosophila melanogaster. Submitted.

Ivan, A., Halfon, M. S. and Sinha, S. (2008). Computational discovery of cis-regulatory modules in Drosophila without prior knowledge of motifs. Genome Biology, 9:R22.

Halfon, M. S., Gallo, S. M. and Bergman, C. M. (2008). REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila. Nucleic Acids Res. 36(Suppl_1):D594-598. doi: 10.1093/nar/gkm876.

Li, L., Zhu, Q., He, X., Sinha, S. and Halfon, M. S. (2007). Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses. Genome Biology, 8:R101

Gallo, S. M., Li, L., Hu, Z. and Halfon, M. S. (2006). REDfly: a regulatory element database for Drosophila. Bioinformatics, 22:381-383. Published online 22 Nov 2005, doi:10.1093/bioinformatics/bti794.