title: Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neural Cell-Fate Determinants Section, NINDS, NIH, Bethesda, Maryland, USA. brodyt@ninds.nih.gov
authors.forename: Thomas
authors.initials: T
authors.lastname: Brody
authors.forename: Wayne
authors.initials: W
authors.lastname: Rasband
authors.forename: Kevin
authors.initials: K
authors.lastname: Baler
authors.forename: Alexander
authors.initials: A
authors.lastname: Kuzin
authors.forename: Mukta
authors.initials: M
authors.lastname: Kundu
authors.forename: Ward F
authors.initials: WF
authors.lastname: Odenwald
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D017124:Conserved Sequence; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D017344:Genes, Insect; D009474:Neurons; D016415:Sequence Alignment; D012984:Software; D013234:Stem Cells; D014157:Transcription Factors / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D014157:Transcription Factors; C482446:nvy protein, Drosophila