Promoter Activation by Enhancer-Dependent and -Independent Loading of Activator and Coactivator Complexes

Abstract

Activation of the pDβ1 promoter at the TCRβ locus requires a functional distal enhancer, Eβ. Here, we have analyzed the mechanism of promoter activation in thymocytes from mice containing or lacking Eβ. We found that pDβ1 shows a complex profile of transcription factor and chromatin remodeling complex occupancy even at Eβ – alleles. The presence of Eβ, however, results in a few specific changes in factor occupancy at the promoter. These differences correlate with localized alterations in histone modifications and in the recruitment of the basal transcriptional machinery. In addition, Eβ is also bound by CBP and Pol II, suggesting a mechanism for delivery of a holoenzyme complex to the pDβ1 promoter. These results illustrate a specialized, long-range function of an enhancer in the hierarchical events that regulate assembly of a cell type-specific promoter.