Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure

Rohit Joshi, Jonathan M. Passner, Remo Rohs, Rinku Jain, Alona Sosinsky, Michael A. Crickmore, Vinitha Jacob, Aneel K. Aggarwal, Barry Honig, Richard S. Mann

Research output: Contribution to journalArticlepeer-review

265 Scopus citations


The recognition of specific DNA-binding sites by transcription factors is a critical yet poorly understood step in the control of gene expression. Members of the Hox family of transcription factors bind DNA by making nearly identical major groove contacts via the recognition helices of their homeodomains. In vivo specificity, however, often depends on extended and unstructured regions that link Hox homeodomains to a DNA-bound cofactor, Extradenticle (Exd). Using a combination of structure determination, computational analysis, and in vitro and in vivo assays, we show that Hox proteins recognize specific Hox-Exd binding sites via residues located in these extended regions that insert into the minor groove but only when presented with the correct DNA sequence. Our results suggest that these residues, which are conserved in a paralog-specific manner, confer specificity by recognizing a sequence-dependent DNA structure instead of directly reading a specific DNA sequence.

Original languageEnglish
Pages (from-to)530-543
Number of pages14
Issue number3
StatePublished - 2 Nov 2007


  • DNA


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