Journal
CELL
Volume 118, Issue 4, Pages 453-464Publisher
CELL PRESS
DOI: 10.1016/j.cell.2004.08.007
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Funding
- NIGMS NIH HHS [R01-GM39458-20] Funding Source: Medline
- PHS HHS [R01-A1042549-061] Funding Source: Medline
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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 affect which coactivators will form productive interactions, with the bound NF-kappaB dinner. This suggests that binding sites may impart a specific configuration to bound transcription factors.
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