title: Cofactor binding evokes latent differences in DNA binding specificity between Hox proteins.
abstract: Members of transcription factor families typically have similar DNA binding specificities yet execute unique functions in vivo. Transcription factors often bind DNA as multiprotein complexes, raising the possibility that complex formation might modify their DNA binding specificities. To test this hypothesis, we developed an experimental and computational platform, SELEX-seq, that can be used to determine the relative affinities to any DNA sequence for any transcription factor complex. Applying this method to all eight Drosophila Hox proteins, we show that they obtain novel recognition properties when they bind DNA with the dimeric cofactor Extradenticle-Homothorax (Exd). Exd-Hox specificities group into three main classes that obey Hox gene collinearity rules and DNA structure predictions suggest that anterior and posterior Hox proteins prefer DNA sequences with distinct minor groove topographies. Together, these data suggest that emergent DNA recognition properties revealed by interactions with cofactors contribute to transcription factor specificities in vivo.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168(th) Street, HHSC 1104, New York, NY 10032, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Slattery
authors.forename: Todd
authors.initials: T
authors.lastname: Riley
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Namiko
authors.initials: N
authors.lastname: Abe
authors.forename: Pilar
authors.initials: P
authors.lastname: Gomez-Alcala
authors.forename: Iris
authors.initials: I
authors.lastname: Dror
authors.forename: Tianyin
authors.initials: T
authors.lastname: Zhou
authors.forename: Remo
authors.initials: R
authors.lastname: Rohs
authors.forename: Barry
authors.initials: B
authors.lastname: Honig
authors.forename: Harmen J
authors.initials: HJ
authors.lastname: Bussemaker
authors.forename: Richard S
authors.initials: RS
authors.lastname: Mann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004247:DNA / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D005821:Genetic Techniques; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C083405:exd protein, Drosophila; D004247:DNA