Diversity and Complexity in DNA Recognition by Transcription Factors

Why did anyone think it would be so simple? Let's first assume complexity and not be surprised when we find it.

Badis G, Berger MF, Philippakis AA, Talukder S, Gehrke AR, Jaeger SA, Chan ET, Metzler G, Vedenko A, Chen X, Kuznetsov H, Wang CF, Coburn D, Newburger DE, Morris Q, Hughes TR, Bulyk ML. Diversity and complexity in DNA recognition by transcription factors. Science. 2009 Jun 26;324(5935):1720-3. [PubMed]

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.