title: Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences.
abstract: Most homeodomains are unique within a genome, yet many are highly conserved across vast evolutionary distances, implying strong selection on their precise DNA-binding specificities. We determined the binding preferences of the majority (168) of mouse homeodomains to all possible 8-base sequences, revealing rich and complex patterns of sequence specificity and showing that there are at least 65 distinct homeodomain DNA-binding activities. We developed a computational system that successfully predicts binding sites for homeodomain proteins as distant from mouse as Drosophila and C. elegans, and we infer full 8-mer binding profiles for the majority of known animal homeodomains. Our results provide an unprecedented level of resolution in the analysis of this simple domain structure and suggest that variation in sequence recognition may be a factor in its functional diversity and evolutionary success.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Gwenael
authors.initials: G
authors.lastname: Badis
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gehrke
authors.forename: Shaheynoor
authors.initials: S
authors.lastname: Talukder
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Philippakis
authors.forename: Lourdes
authors.initials: L
authors.lastname: Peña-Castillo
authors.forename: Trevis M
authors.initials: TM
authors.lastname: Alleyne
authors.forename: Sanie
authors.initials: S
authors.lastname: Mnaimneh
authors.forename: Olga B
authors.initials: OB
authors.lastname: Botvinnik
authors.forename: Esther T
authors.initials: ET
authors.lastname: Chan
authors.forename: Faiqua
authors.initials: F
authors.lastname: Khalid
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Daniel
authors.initials: D
authors.lastname: Newburger
authors.forename: Savina A
authors.initials: SA
authors.lastname: Jaeger
authors.forename: Quaid D
authors.initials: QD
authors.lastname: Morris
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D011485:Protein Binding; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D014157:Transcription Factors; D004247:DNA