Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences

被引：511

作者：

Berger, Michael F. ^{[1
]}

Badis, Gwenael ^{[5
]}

Gehrke, Andrew R. ^{[1
]}

Talukder, Shaheynoor ^{[5
]}

Philippakis, Anthony A. ^{[1
,6
]}

Pena-Castillo, Lourdes ^{[4
]}

Alleyne, Trevis M. ^{[5
]}

Mnaimneh, Sanie ^{[4
]}

Botvinnik, Olga B. ^{[1
,7
]}

Chan, Esther T. ^{[5
]}

Khalid, Faiqua ^{[4
]}

Zhang, Wen ^{[5
]}

Newburger, Daniel ^{[1
]}

Jaeger, Savina A. ^{[1
]}

Morris, Quaid D. ^{[4
,5
]}

Bulyk, Martha L. ^{[1
,2
,3
,6
]}

Hughes, Timothy R. ^{[4
,5
]}

机构：

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

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

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

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

[5] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 3E1, Canada

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

[7] MIT, Dept Math, Cambridge, MA 02139 USA

来源：

CELL | 2008年 / 133卷 / 07期

关键词：

D O I：

10.1016/j.cell.2008.05.024

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：1266 / 1276

页数：11

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