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Eukaryotes transcribe much of their genomes, but little is known about the fidelity of transcriptional initiation by RNA polymerase II in vivo. I suggest that ∼90% of Pol II initiation events in yeast represent transcriptional noise, and that the specificity of initiation is comparable to that of DNA-binding proteins and other biological processes. This emphasizes the need to develop criteria that distinguish transcriptional noise from transcription with a biological function.
