REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila

Abstract

The identification and study of the cis-regulatory elements that control gene expression are important areas of biological research, but few resources exist to facilitate large-scale bioinformatics studies of cis-regulation in metazoan species. Drosophila melanogaster, with its well-annotated genome, exceptional resources for comparative genomics and long history of experimental studies of transcriptional regulation, represents the ideal system for regulatory bioinformatics. We have merged two existing Drosophila resources, the REDfly database of cis-regulatory modules and the FlyReg database of transcription factor binding sites (TFBSs), into a single integrated database containing extensive annotation of empirically validated cis-regulatory modules and their constituent binding sites. With the enhanced functionality made possible through this integration of TFBS data into REDfly, together with additional improvements to the REDfly infrastructure, we have constructed a one-stop portal for Drosophila cis-regulatory data that will serve as a powerful resource for both computational and experimental studies of transcriptional regulation. REDfly is freely accessible at http://redfly.ccr.buffalo.edu.

Figure 1.

Searching for regulatory elements based on the expression patterns they regulate using the ‘Ontology’ search function. Clicking on the ‘Browse Ontology’ button (circled) will open a pop-up window with the ontology tree (inset) that can then be navigated until the desired anatomical feature at the preferred level of granularity is reached. All REDfly records annotated with the selected term or any of its descendant terms will be returned in the database search. In the pictured example, the chosen term is ‘somatic muscle primordium’; any records containing annotations for ‘somatic muscle primordium’ or its two descendant terms ‘embryonic somatic muscle’ and ‘larval somatic muscle’ will be returned. Alternatively, a user can type a term into the ‘Expression Term or Id’ field, in which case only records annotated with that term (e.g., ‘somatic muscle primordium’) will be returned.

Figure 2.

Integration of CRM and TFBS records. An exciting new feature in REDfly is its cross-referencing of CRMs with any TFBSs that fall within them. Panel A shows the detailed view page for the CRM Dll_208, which contains three footprinted TFBSs with records in REDfly. The arrow indicates the link to the record for one of these three TFBSs, Ubx_Dll:REDFLY:TF000513. Panel B shows the record obtained through the link indicated in panel A. Note that the lookup is functional in both directions; from this TFBS record page, there is a link to the CRM in which the binding site is located (arrow).