Variable structure motifs for transcription factor binding sites

Reid, J.E. and Evans, Kenneth J. and Dyer, N. and Wernisch, Lorenz and Ott, S. (2010) Variable structure motifs for transcription factor binding sites. BMC Genomics 11 (1), p. 30. ISSN 1471-2164.

Abstract

Classically, models of DNA-transcription factor binding sites (TFBSs) have been based on relatively few known instances and have treated them as sites of fixed length using position weight matrices (PWMs). Various extensions to this model have been proposed, most of which take account of dependencies between the bases in the binding sites. However, some transcription factors are known to exhibit some flexibility and bind to DNA in more than one possible physical configuration. In some cases this variation is known to affect the function of binding sites. With the increasing volume of ChIP-seq data available it is now possible to investigate models that incorporate this flexibility. Previous work on variable length models has been constrained by: a focus on specific zinc finger proteins in yeast using restrictive models; a reliance on hand-crafted models for just one transcription factor at a time; and a lack of evaluation on realistically sized data sets.

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