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Open Access Research article

Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

Thomas Brody1, Wayne Rasband2, Kevin Baler2, Alexander Kuzin1, Mukta Kundu1 and Ward F Odenwald1*

Author Affiliations

1 Neural Cell-Fate Determinants Section, NINDS, NIH, Bethesda, Maryland, USA

2 Office of Scientific Director, IRP, NIMH, NIH, Bethesda, Maryland, USA

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BMC Genomics 2008, 9:371  doi:10.1186/1471-2164-9-371

Published: 1 August 2008

Abstract

Background

The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers.

Results

Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs) made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS.

Conclusion

The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.