Simple CRP regulation operates through two related mechanisms, designated class I and class II. Both classes depend on specific interactions between CRP and RNAP. At class I promoters, a CRP dimer (cross-hatched double oval) binds to DNA at a site centered near position −61.5, −71.5, −82.5, or −92.5. Simple CRP regulation operates through two related mechanisms, designated class I and class II. Both classes depend on specific interactions between CRP and RNAP. At class I promoters, a CRP dimer (cross-hatched double oval) binds to DNA at a site centered near position −61.5, −71.5, −82.5, or −92.5. CRP bound at any of these positions uses a defined surface (activating region 1 [AR1]) in the downstream subunit of CRP to contact a specific surface determinant (287) of the C-terminal domain of the α-subunit of RNAP (α-CTD; gray double oval). Two additional α-CTD determinants contribute to class I activation: the 261 determinant, proposed to interact with the σ subunit of RNAP (checkered shape), and the 265 determinant, which binds DNA, preferably A+T-rich sequences, e.g., the UP element. At class II promoters, a CRP dimer binds to DNA at a site centered near position −41.5. When bound at this position, CRP uses AR1 of the upstream subunit of CRP to contact determinant 287 of the α-CTD. CRP uses a second surface (AR2) of the downstream subunit to contact the 162-165 determinant of the N-terminal domain of α. The 265 determinant of the α-CTD also contributes by binding DNA. Class III promoters use more complex mechanisms that utilize two CRP dimers to achieve maximal transcription activation. In class III activation, the CRP dimers can bind either to tandem class I positions (as is the case at acs) or to one class II and one class I position. For reviews, see references 64, 69, and 158. Alan J. Wolfe Microbiol. Mol. Biol. Rev. 2005; doi:10.1128/MMBR.69.1.12-50.2005