The transcriptional specificity of NF-?B dimers is coded within the ?B DNA response elements.

ABSTRACT: Nuclear factor ?B (NF-?B) regulates gene expression by binding to specific DNA elements, known collectively as ?B sites, that are contained within the promoters/enhancers of target genes. We found that the identity of the central base pair (bp) of ?B sites profoundly affects the transcriptional activity of NF-?B dimers. RelA dimers prefer an A/T bp at this position for optimal transcriptional activation (A/T-centric) and discriminate against G/C-centric ?B sites. The p52 homodimer, in contrast, activates transcription from G/C-centric ?B sites in complex with Bcl3 but represses transcription from the A/T-centric sites. The p52:Bcl3 complex binds to these two classes of ?B 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 ?B sites, NF-?B dimers modulate biological programs by activating, repressing, and altering the expression of effector genes.

SUBMITTER: Wang VY 

PROVIDER: S-EPMC4167904 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature