Diversity and complexity in DNA recognition by transcription factors.
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.
Badis
Gwenael
G
Banting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada.
Berger
Michael F
MF
Philippakis
Anthony A
AA
Talukder
Shaheynoor
S
Gehrke
Andrew R
AR
Jaeger
Savina A
SA
Chan
Esther T
ET
Metzler
Genita
G
Vedenko
Anastasia
A
Chen
Xiaoyu
X
Kuznetsov
Hanna
H
Wang
Chi-Fong
CF
Coburn
David
D
Newburger
Daniel E
DE
Morris
Quaid
Q
Hughes
Timothy R
TR
Bulyk
Martha L
ML
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*
D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D004247:DNA