Mechanism for a transcriptional activator that works at the isomerization step

Transcriptional activators in prokaryotes have been shown to stimulate diff erent steps in the initiation process including the initial binding of RNA polymerase (RNAP) to the promoter and a postbinding step known as the isome rization step. Evidence suggests that activators that affect initial bindin g can work by a cooperative binding mechanism by making energetically favor able contacts with RNAP, but the mechanism by which activators affect the i somerization step is unclear. A well-studied example of an activator that n ormally exerts its effect exclusively on the isomerization step is the bact eriophage lambda cl protein (lambda cl), which has been shown genetically t o interact with the C-terminal region of the sigma (70) subunit of RNAP, We show here that the interaction between hcl and sigma can stimulate transcr iption even when the relevant portion of sigma is transplanted to another s ubunit of RNAP, This activation depends on the ability of Acl to stabilize the binding of the transplanted sigma moiety to an ectopic -35 element. Bas ed on these and previous findings, we discuss a simple model that explains how an activator's ability to stabilize the binding of an RNAP subdomain to the DNA can account for its effect on either the initial binding of RNAP t o a promoter or the isomerization step.