The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements.
Nuclear factor κB (NF-κB) regulates gene expression by binding to specific DNA elements, known collectively as κB sites, that are contained within the promoters/enhancers of target genes. We found that the identity of the central base pair (bp) of κB sites profoundly affects the transcriptional activity of NF-κB dimers. RelA dimers prefer an A/T bp at this position for optimal transcriptional activation (A/T-centric) and discriminate against G/C-centric κB sites. The p52 homodimer, in contrast, activates transcription from G/C-centric κB sites in complex with Bcl3 but represses transcription from the A/T-centric sites. The p52:Bcl3 complex binds to these two classes of κB sites in distinct modes, permitting the recruitment of coactivator, corepressor, or both coactivator and corepressor complexes in promoters that contain G/C-, A/T-, or both G/C- and A/T-centric sites. Therefore, through sensing of bp differences within κB sites, NF-κB dimers modulate biological programs by activating, repressing, and altering the expression of effector genes.
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Vivien Ya-Fan
VY
Wang
Wendy
W
Huang
Masataka
M
Asagiri
Nathanael
N
Spann
Alexander
A
Hoffmann
Christopher
C
Glass
Gourisankar
G
Ghosh
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D020218:Response Elements; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins; D051996:Transcription Factor RelA; D014157:Transcription Factors; D004247:DNA