Transcription activation at Class II CAP‐dependent promoters

Abstract

Transcription activation at Class II CAP‐dependent promoters provides a paradigm for understanding how a single activator molecule can make multiple interactions with the transcription machinery, with each interaction being responsible for a specific mechanistic consequence. At Class II CAP‐dependent promoters, the DNA target site for CAP is centred near position −42, overlapping and replacing the −35 determinant for binding of RNA polymerase (RNAP). Transcription activation requires two distinct mechanistic components. The first component is ‘anti‐inhibition,’ overcoming an inhibitory effect of the RNAP α subunit C‐terminal domain (αCTD). This component involves direct contact between amino acids 156–164 (activating region 1) of the upstream subunit of the CAP dimer and a target in αCTD. The second component is ‘direct activation’, facilitating isomerization of the RNAP–promoter closed complex to the transcriptionally competent open complex. This component involves direct contact between amino acids 19, 21 and 101 (activating region 2) of the downstream subunit of the CAP dimer and a target in the RNAP α subunit N‐terminal domain (αNTD).