@article{1fc66441d50048a49fae4d9a0569e9f3,
title = "Functional Specificity of a Hox Protein Mediated by the Recognition of Minor Groove Structure",
abstract = "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.",
keywords = "DEVBIO, DNA, PROTEINS",
author = "Rohit Joshi and Passner, {Jonathan M.} and Remo Rohs and Rinku Jain and Alona Sosinsky and Crickmore, {Michael A.} and Vinitha Jacob and Aggarwal, {Aneel K.} and Barry Honig and Mann, {Richard S.}",
note = "Funding Information: We thank D. Andrew and S. Beckendorf for reagents, D. Andrew for advice on the Creb and Fkh stains, and D. Andrew, L. Shapiro, and T. Jessell for comments on the manuscript. We thank P. Wright for pointing out the importance of RGR and RGGR motifs in human orphan estrogen receptors. This work was supported by NIH grants GM62947 and AI41706 to A.K.A., GM074105 and GM54510 to R.S.M., and an NIH U54 CA121852 MAGNet grant. Author contributions: R. Joshi constructed the mutants and carried out the DNA-binding and in vivo experiments; J.M.P. and R. Jain solved the X-ray structures; A.S. and R.R. carried out the computational work; R.S.M., B.H., A.A., and R.R. wrote the paper. M.A.C. and V.J. made contributions to the fly genetics and crystallography, respectively. ",
year = "2007",
month = nov,
day = "2",
doi = "10.1016/j.cell.2007.09.024",
language = "English",
volume = "131",
pages = "530--543",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}