68 Deconvoluting the recognition of DNA shape from DNA sequence

In previous work (Slattery et al., 2011; Joshi et al., 2007), we described the importance of the 3-D structure of the DNA double helix – DNA shape – in the recognition of DNA binding sites by the Hox family of transcription factors. In particular, we found that local minima in the width of the DNA minor groove create electronegative pockets that are binding sites for amino acids with positively-charged side chains such as arginine. Moreover, our data argued that DNA shape is a consequence of DNA sequence, and thus led to the idea that the recognition of specific DNA sequences by DNA binding proteins is mediated by both base-readout, typically in the major groove, and shape-readout (Rohs et al., 2010). The relationship between DNA shape and DNA sequence leads to a logical loop that is difficult to tease apart: if shape is a consequence of sequence, then is the recognition of a binding site by a transcription factor mediated by the sequence of base pairs or by the resulting shape of the DNA molecule? One pr...