Sequence conservation and combinatorial complexity of <it>Drosophila </it>neural precursor cell enhancers

• Main Authors: Kuzin Alexander, Baler Kevin, Rasband Wayne, Brody Thomas, Kundu Mukta, Odenwald Ward F
• Format: Article
• Language: English
• Published: BMC 2008-08-01
• Series: BMC Genomics
• Online Access: http://www.biomedcentral.com/1471-2164/9/371

<p>Abstract</p> <p>Background</p> <p>The presence of highly conserved sequences within <it>cis</it>-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 <it>Drosophila </it>neural development. We describe the use of <it>EvoPrinter </it>and <it>cis</it>-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers.</p> <p>Results</p> <p>Analysis of <it>in vivo </it>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 <it>nervy </it>gene in neural precursor cells of the CNS and PNS.</p> <p>Conclusion</p> <p>The combined use <it>EvoPrinter </it>and <it>cis</it>-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.</p>