c-Myc regulates transcriptional pause release

Recruitment of the RNA polymerase II (Pol II) transcription initiation apparatus to promoters by specific DNA-binding transcription factors is well recognized as a key regulatory step in gene expression. We report here that promoter-proximal pausing is a general feature of transcription by Pol II in mammalian cells and thus an additional step where regulation of gene expression occurs. This suggests that some transcription factors recruit the transcription apparatus to promoters, whereas others effect promoter-proximal pause release. Indeed, we find that the transcription factor c-Myc, a key regulator of cellular proliferation, plays a major role in Pol II pause release rather than Pol II recruitment at its target genes. We discuss the implications of these results for the role of c-Myc amplification in human cancer.National Institutes of Health (U.S.) (Grant number RO1-HG002668)National Institutes of Health (U.S.) (Grant number RO1-GM34277)National Institutes of Health (U.S.) (Grant number RO1-CA133404)National Cancer Institute (U.S.) (Grant Number PO1- CA42063)National Cancer Institute (U.S.) Cancer Center Support Grant (Grant Number P30-CA14051)National Institutes of Health (U.S.) Postdoctoral Fellowship (5-F32-HD051190