RNA polymerase II C-terminal domain required for enhancer-driven transcription

The RNA polymerase II carboxy-terminal domain (CTD) consists of tandem repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser^1-3. The CTD may participate in activated transcription through interaction with a high-molecular-weight mediator complex^4-6. Such a role would be consistent with observations that some genes are preferentially sensitive to CTD mutations^7,8. Here we investigate the function of the mouse RNA polymerase CTD in enhancer-driven transcription. Transcription by α-amanitin-resistant CTD-deletion mutants was tested by transient transfection of tissue culture cells in the presence of α-amanitin in order to inhibit endogenous RNA polymerase II. Removal of most of the CTD abolishes transcriptional activation by all enhancers tested, whereas transcription from promoters driven by Spl, a factor that typically activates housekeeping genes from positions proximal to the initiation sites, is not affected. These findings show that the CTD is essential in mediating 'enhancer'-type activation of mammalian transcription.