期刊
CELL
卷 131, 期 3, 页码 530-543出版社
CELL PRESS
DOI: 10.1016/j.cell.2007.09.024
关键词
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资金
- NCI NIH HHS [U54 CA121852] Funding Source: Medline
- NIAID NIH HHS [AI41706, R01 AI041706] Funding Source: Medline
- NIGMS NIH HHS [GM54510, R01 GM054510-15, R01 GM054510, R01 GM054510-14, R01 GM054510-16, R01 GM062947, R24 GM074105-03, GM074105, R01 GM054510-13, R24 GM074105-04, GM62947, R24 GM074105] Funding Source: Medline
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.
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