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Molecular and Cellular Biology, November 2004, p. 9517-9526, Vol. 24, No. 21
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.21.9517-9526.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Proneural Proteins Atonal and Scute Regulate Neural Target Genes through Different E-Box Binding Sites

Lynn M. Powell, Petra I. zur Lage, David R. A. Prentice, Biruntha Senthinathan, and Andrew P. Jarman*

Division of Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom

Received 30 July 2004/ Accepted 6 August 2004

For a particular functional family of basic helix-loop-helix (bHLH) transcription factors, there is ample evidence that different factors regulate different target genes but little idea of how these different target genes are distinguished. We investigated the contribution of DNA binding site differences to the specificities of two functionally related proneural bHLH transcription factors required for the genesis of Drosophila sense organ precursors (Atonal and Scute). We show that the proneural target gene, Bearded, is regulated by both Scute and Atonal via distinct E-box consensus binding sites. By comparing with other Ato-dependent enhancer sequences, we define an Ato-specific binding consensus that differs from the previously defined Scute-specific E-box consensus, thereby defining distinct EAto and ESc sites. These E-box variants are crucial for function. First, tandem repeats of 20-bp sequences containing EAto and ESc sites are sufficient to confer Atonal- and Scute-specific expression patterns, respectively, on a reporter gene in vivo. Second, interchanging EAto and ESc sites within enhancers almost abolishes enhancer activity. While the latter finding shows that enhancer context is also important in defining how proneural proteins interact with these sites, it is clear that differential utilization of DNA binding sites underlies proneural protein specificity.

* Corresponding author. Mailing address: Division of Biomedical Sciences, University of Edinburgh, George Square, Edinburgh EH8 9XD, United Kingdom. Phone: 44(0)131 650 373. Fax: 44(0)131 650 6527. E-mail: andrew.jarman{at}ed.ac.uk.

Molecular and Cellular Biology, November 2004, p. 9517-9526, Vol. 24, No. 21
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.21.9517-9526.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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