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Cell. 2004 Aug 20;118(4):453-64.

One nucleotide in a kappaB site can determine cofactor specificity for NF-kappaB dimers.

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1
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.

Abstract

The transcription factor NF-kappaB regulates a wide variety of genes involved in multiple processes. Although the apparent consensus sequence of DNA binding sites for NF-kappaB (kappaB sites) is very broad, the sites active in any one gene show remarkable evolutionary stability. Using a lentivirus-based methodology for implantation of gene regulatory sequences we show that for genes with two kappaB sites, both are required for activity. Swapping sites between kappaB-dependent genes altered NF-kappaB dimer specificity of the promoters and revealed that two kappaB sites can function together as a module to regulate gene activation. Further, although the sequence of the kappaB site is important for determining kappaB family member specificity, rather than determining the ability of a particular dimer to bind effectively, the sequence affects which coactivators will form productive interactions with the bound NF-kappaB dimer. This suggests that binding sites may impart a specific configuration to bound transcription factors.

PMID:
15315758
DOI:
10.1016/j.cell.2004.08.007
[Indexed for MEDLINE]
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