Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences.
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.
Berger
Michael F
MF
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Badis
Gwenael
G
Gehrke
Andrew R
AR
Talukder
Shaheynoor
S
Philippakis
Anthony A
AA
Peña-Castillo
Lourdes
L
Alleyne
Trevis M
TM
Mnaimneh
Sanie
S
Botvinnik
Olga B
OB
Chan
Esther T
ET
Khalid
Faiqua
F
Zhang
Wen
W
Newburger
Daniel
D
Jaeger
Savina A
SA
Morris
Quaid D
QD
Bulyk
Martha L
ML
Hughes
Timothy R
TR
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
D018398:Homeodomain Proteins; D014157:Transcription Factors; D004247:DNA