Diversity and Complexity in DNA Recognition by Transcription Factors

被引：726

作者：

Badis, Gwenael ^{[1
]}

Berger, Michael F. ^{[2
,4
]}

Philippakis, Anthony A. ^{[2
,3
,4
]}

Talukder, Shaheynoor ^{[1
,5
]}

Gehrke, Andrew R. ^{[2
]}

Jaeger, Savina A. ^{[2
]}

Chan, Esther T. ^{[5
]}

Metzler, Genita ^{[6
]}

Vedenko, Anastasia ^{[7
]}

Chen, Xiaoyu ^{[1
]}

Kuznetsov, Hanna ^{[6
]}

Wang, Chi-Fong ^{[8
]}

Coburn, David ^{[1
]}

Newburger, Daniel E. ^{[2
]}

Morris, Quaid ^{[1
,5
,9
,10
]}

Hughes, Timothy R. ^{[1
,5
,10
]}

Bulyk, Martha L. ^{[2
,3
,4
,11
]}

机构：

[1] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1, Canada

[2] Brigham & Womens Hosp, Div Genet, Dept Med, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA

[4] Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA

[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

[6] MIT, Dept Biol, Cambridge, MA 02139 USA

[7] Wellesley Coll, Dept Biol, Wellesley, MA 02481 USA

[8] MIT, Dept Phys, Cambridge, MA 02139 USA

[9] Univ Toronto, Dept Comp Sci, Toronto, ON M5S 3G4, Canada

[10] Univ Toronto, Terrence Donnelly Ctr Cellular & Biomol Res, Toronto, ON M5S 3E1, Canada

[11] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

SCIENCE | 2009年 / 324卷 / 5935期

基金：

加拿大健康研究院;

关键词：

BINDING SPECIFICITIES; GENE-REGULATION; PROTEIN; SEQUENCE; REPRESSOR; IDENTIFICATION; MICROARRAYS; EXPRESSION; DOMAIN; SITES;

D O I：

10.1126/science.1162327

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1720 / 1723

页数：4

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