Figure 9.

A model of the mechanism through which p65 epigenetically affects gene expression. Upon stimulation, p50:p65 heterodimers containing phosphorylated p65 at Ser 276 enter the nucleus and recruit the transcription coactivator CBP/p300 to κB-binding sites on DNA, leading to normal gene transcription. In contrast, p50:p65–RRPA heterodimers lacking phosphorylation of Ser 276 cannot bind to CBP/p300 efficiently and instead recruit HDAC3 corepressor complexes to DNA, resulting in direct repression of a subset of NF-κB target genes and repression of non-NF-κB-regulated genes through epigenetic mechanisms. p50:p65–RAPA heterodimers cannot bind to DNA and thus cannot mediate the epigenetic effects induced by RRPA mutant p65.