OnTheFly: a database of Drosophila melanogaster transcription factors and their binding sites

Abstract

We present OnTheFly (http://bhapp.c2b2.columbia.edu/OnTheFly/index.php), a database comprising a systematic collection of transcription factors (TFs) of Drosophila melanogaster and their DNA-binding sites. TFs predicted in the Drosophila melanogaster genome are annotated and classified and their structures, obtained via experiment or homology models, are provided. All known preferred TF DNA-binding sites obtained from the B1H, DNase I and SELEX methodologies are presented. DNA shape parameters predicted for these sites are obtained from a high throughput server or from crystal structures of protein-DNA complexes where available. An important feature of the database is that all DNA-binding domains and their binding sites are fully annotated in a eukaryote using structural criteria and evolutionary homology. OnTheFly thus provides a comprehensive view of TFs and their binding sites that will be a valuable resource for deciphering non-coding regulatory DNA.

Figure 1.

The contribution of previous databases to the PWMs appearing in OnTheFly.

Figure 2.

TF search workflow in OnTheFly. This figure describes a search for a sequence-specific transcription factor, Homeotic protein Deformed (DFD). (A) In the Entry Screen, we choose TF search. (B) A search for the term Deformed retrieves six TFs. (C) Choosing the second, DFD_DROME, leads to a detailed TF screen. This screen shows that DFD possesses a homeodomain and has two known TFBS represented by a PWM, one based on B1H data and the other based on DNase I data. (D) A homology model for this protein shows three alpha helices comprising the homeodomain shown using the MarkUs viewer. (E) The DNA sequences retrieved by DNase I are sorted according to their putative binding affinity to this protein. (F) Opening the DNaseI or B1H links shows the results of the DNA shape server (30). Each line in the graph represents the minor groove width along a different DNA sequence, which was entered as input. The graph shows that most of the sequences possess a minimum in width (narrower minor groove width in the AT part of the DNA sequence motif).