Conserved cAMP responsive element and core promoter complex are critical for specificity of the distal T-cell receptor beta chain enhancer for its native promoter.
The Vbeta 8.1 promoter is regulated by T-cell-specific and ubiquitous transcription factors, which bind immediately upstream of and inside the core promoter region. The various Vbeta promoters contain two conserved elements, a cAMP responsive element (CRE) located upstream of the core promoter and a basal initiator flanked by two regulatory motifs. Here we have studied the interplay between the distal enhancer and its native promoter. We show that the remote enhancer acts specifically through its native promoter. Specific enhancer-promoter interplay is mediated through the conserved regions of the Vbeta promoters. Importantly, the conserved CRE serves as a functional recognition element for the enhancer whereas it barely contributes to promoter activity. The other conserved regions surrounding the initiation site are critical for activators that bind at and function through the core promoter region and thereby regulate both promoter and enhancer activity. The enhancer is highly sensitive to E1A-12S, which represses both general and specific enhancer activities. Enhancer activity and promoter-enhancer specificity is, at least in part, mediated by the coactivators CBP/p300.
Haus-Seuffert
P
P
Laboratorium für Molekulare Biologie, Genzentrum, der Ludwig-Maximilians-Universität, D-81377, München, Germany.
Halle
J P
JP
Sanner
S
S
Meisterernst
M
M
D017500:Adenovirus E1A Proteins / Q000494:pharmacology; D050882:CREB-Binding Protein; D017124:Conserved Sequence; D004742:Enhancer Elements, Genetic; D017930:Genes, Reporter; D019674:Genes, T-Cell Receptor beta / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D008957:Models, Genetic; D016296:Mutagenesis; D009687:Nuclear Proteins / Q000502:physiology*; D010703:Phorbol Esters / Q000494:pharmacology; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D015534:Trans-Activators / Q000502:physiology*; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D009687:Nuclear Proteins; D010703:Phorbol Esters; D015534:Trans-Activators; C119222:phorbol-12-myristate; D050882:CREB-Binding Protein; C494363:CREBBP protein, human