Fig. 6

Schematic representation of the molecular heterogeneity and differential roles of Fra-1 and p300/CBP at the TGFB2 PIRs. This model shows various types of PIRs: (1) Fra-1 modulates the recruitment of p300/CBP, whose presence but not the KAT activity is required for enhancer activity (e.g. enhancer at + 136 kb). (2) Fra-1 inhibits p300/CBP KAT activity which is important for enhancer activation (e.g. enhancer at + 151 kb), (3) enhancer activity depends on p300/CBP KAT activity but not on Fra-1 (e.g. enhancer at + 360 kb), (4) Fra-1 enhances eRNA production independently of p300/CBP KAT activity, (5) neither Fra-1 nor p300/CBP affects enhancer activity (e.g. enhancer at + 980 kb) and (6) CTCF-bound PIR contributing to the structural organization of this locus. The overall activity of Fra-1 at these enhancers inhibits Pol II-Ser5 phosphorylation, limiting transcription initiation at TGFB2 promoter. Fra-1 is indicated in purple and its dimerization partner in green. Violet arrows indicate the positive/negative effects of Fra-1 whereas the green and red arrows indicate KAT-independent- and KAT-dependent effects of P300/CBP in eRNA production, respectively