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Published online before print February 15, 2002, 10.1101/gr.212502. Article published online before print in February 2002
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Vol. 12, Issue 3, 470-481, March 2002

METHODS
Extraction of Functional Binding Sites from Unique Regulatory Regions: The Drosophila Early Developmental Enhancers

Dmitri A. Papatsenko,1,5 Vsevolod J. Makeev,2 Alex P. Lifanov,3 Mireille Régnier,4 Anna G. Nazina,1 and Claude Desplan1

1 Department of Biology, New York University, New York, New York, 10003-6688, USA; 2 State Scientific Center Genetika, Moscow 113545, Russia; 3 Institute of Chemical Physics, Moscow 117421, Russia; 4  Institut National de Recherche en Informatique et en Automatique Rocquencourt, 78153, Le Chesnay Cedex, France

The early developmental enhancers of Drosophila melanogaster comprise one of the most sophisticated regulatory systems in higher eukaryotes. An elaborate code in their DNA sequence translates both maternal and early embryonic regulatory signals into spatial distribution of transcription factors. One of the most striking features of this code is the redundancy of binding sites for these transcription factors (BSTF). Using this redundancy, we explored the possibility of predicting functional binding sites in a single enhancer region without any prior consensus/matrix description or evolutionary sequence comparisons. We developed a conceptually simple algorithm, Scanseq, that employs an original statistical evaluation for identifying the most redundant motifs and locates the position of potential BSTF in a given regulatory region. To estimate the biological relevance of our predictions, we built thorough literature-based annotations for the best-known Drosophila developmental enhancers and we generated detailed distribution maps for the most robust binding sites. The high statistical correlation between the location of BSTF in these experiment-based maps and the location predicted in silico by Scanseq confirmed the relevance of our approach. We also discuss the definition of true binding sites and the possible biological principles that govern patterning of regulatory regions and the distribution of transcriptional signals.

5 Corresponding author.

12:470-481 ©2002 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/02 $5.00
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