Abstract:
:Protein-DNA binding is mediated by the recognition of the chemical signatures of the DNA bases and the 3D shape of the DNA molecule. Because DNA shape is a consequence of sequence, it is difficult to dissociate these modes of recognition. Here, we tease them apart in the context of Hox-DNA binding by mutating residues that, in a co-crystal structure, only recognize DNA shape. Complexes made with these mutants lose the preference to bind sequences with specific DNA shape features. Introducing shape-recognizing residues from one Hox protein to another swapped binding specificities in vitro and gene regulation in vivo. Statistical machine learning revealed that the accuracy of binding specificity predictions improves by adding shape features to a model that only depends on sequence, and feature selection identified shape features important for recognition. Thus, shape readout is a direct and independent component of binding site selection by Hox proteins.
journal_name
Celljournal_title
Cellauthors
Abe N,Dror I,Yang L,Slattery M,Zhou T,Bussemaker HJ,Rohs R,Mann RSdoi
10.1016/j.cell.2015.02.008subject
Has Abstractpub_date
2015-04-09 00:00:00pages
307-18issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(15)00173-7journal_volume
161pub_type
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