title: Diversity and complexity in DNA recognition by transcription factors.
abstract: Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.
authors.affiliation: Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Badis
authors.forename: Michael F
authors.initials: MF
authors.lastname: Berger
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Philippakis
authors.forename: Shaheynoor
authors.initials: S
authors.lastname: Talukder
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gehrke
authors.forename: Savina A
authors.initials: SA
authors.lastname: Jaeger
authors.forename: Esther T
authors.initials: ET
authors.lastname: Chan
authors.forename: Genita
authors.initials: G
authors.lastname: Metzler
authors.forename: Anastasia
authors.initials: A
authors.lastname: Vedenko
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Chen
authors.forename: Hanna
authors.initials: H
authors.lastname: Kuznetsov
authors.forename: Chi-Fong
authors.initials: CF
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Coburn
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Newburger
authors.forename: Quaid
authors.initials: Q
authors.lastname: Morris
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Hughes
authors.forename: Martha L
authors.initials: ML
authors.lastname: Bulyk
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D040081:Protein Array Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA