Mechanism by which the IFN-beta enhanceosome activates transcription.
We demonstrate that in contrast to previous findings by using simple synthetic promoters or activators, the natural IFN-beta enhanceosome activates transcription by causing a dramatic increase of the rate by which preinitiation complexes assemble at the promoter. This effect totally depends on the recruitment of the CBP-PolII holoenzyme by the enhanceosome, because its depletion from the extract decelerates the rate of transcription. However, addition of the CBP-PolII holoenzyme back to these extracts fully restores the speed by which the enhanceosome activates transcription. Strikingly, preincubation of the enhanceosome with the CBP-RNA PolII holoenzyme complex results in instant assembly of preinitiation complexes. In contrast, individual IFN-beta gene activators function solely by increasing the number of functional preinitiation complexes and not the rate of their assembly. Thus, fast recruitment of the CBP-RNA PolII holoenzyme complex is critical for the rapid activation of IFN-beta gene expression by virus infection.
Yie
J
J
Department of Biochemistry, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Senger
K
K
Thanos
D
D
D004742:Enhancer Elements, Genetic; D006367:HeLa Cells; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012320:RNA Polymerase III / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D009687:Nuclear Proteins; D015534:Trans-Activators; D016899:Interferon-beta; D012320:RNA Polymerase III