title: Use of a Drosophila genome-wide conserved sequence database to identify functionally related cis-regulatory enhancers.
abstract: BACKGROUND
  Phylogenetic footprinting has revealed that cis-regulatory enhancers consist of conserved DNA sequence clusters (CSCs). Currently, there is no systematic approach for enhancer discovery and analysis that takes full-advantage of the sequence information within enhancer CSCs.
  
  
  RESULTS
  We have generated a Drosophila genome-wide database of conserved DNA consisting of >100,000 CSCs derived from EvoPrints spanning over 90% of the genome. cis-Decoder database search and alignment algorithms enable the discovery of functionally related enhancers. The program first identifies conserved repeat elements within an input enhancer and then searches the database for CSCs that score highly against the input CSC. Scoring is based on shared repeats as well as uniquely shared matches, and includes measures of the balance of shared elements, a diagnostic that has proven to be useful in predicting cis-regulatory function. To demonstrate the utility of these tools, a temporally-restricted CNS neuroblast enhancer was used to identify other functionally related enhancers and analyze their structural organization.
  
  
  CONCLUSIONS
  cis-Decoder reveals that co-regulating enhancers consist of combinations of overlapping shared sequence elements, providing insights into the mode of integration of multiple regulating transcription factors. The database and accompanying algorithms should prove useful in the discovery and analysis of enhancers involved in any developmental process.
authors.affiliation: Neural Cell-Fate Determinants Section, NINDS, NIH, Bethesda, Maryland 20892, USA. brodyt@ninds.nih.gov
authors.forename: Thomas
authors.initials: T
authors.lastname: Brody
authors.forename: Amarendra S
authors.initials: AS
authors.lastname: Yavatkar
authors.forename: Alexander
authors.initials: A
authors.lastname: Kuzin
authors.forename: Mukta
authors.initials: M
authors.lastname: Kundu
authors.forename: Leonard J
authors.initials: LJ
authors.lastname: Tyson
authors.forename: Jermaine
authors.initials: J
authors.lastname: Ross
authors.forename: Tzu-Yang
authors.initials: TY
authors.lastname: Lin
authors.forename: Chi-Hon
authors.initials: CH
authors.lastname: Lee
authors.forename: Takeshi
authors.initials: T
authors.lastname: Awasaki
authors.forename: Tzumin
authors.initials: T
authors.lastname: Lee
authors.forename: Ward F
authors.initials: WF
authors.lastname: Odenwald
mesh_terms: D000465:Algorithms; D000818:Animals; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics*; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D049750:Genome, Insect; D008969:Molecular Sequence Data; D010802:Phylogeny; D019076:Transgenes