Immediate mediators of the inflammatory response are poised for gene activation through RNA polymerase II stalling.

ABSTRACT: The kinetics and magnitude of cytokine gene expression are tightly regulated to elicit a balanced response to pathogens and result from integrated changes in transcription and mRNA stability. Yet, how a single microbial stimulus induces peak transcription of some genes (TNFalpha) within minutes whereas others (IP-10) require hours remains unclear. Here, we dissect activation of several lipopolysaccharide (LPS)-inducible genes in macrophages, an essential cell type mediating inflammatory response in mammals. We show that a key difference between the genes is the step of the transcription cycle at which they are regulated. Specifically, at TNFalpha, RNA Polymerase II initiates transcription in resting macrophages, but stalls near the promoter until LPS triggers rapid and transient release of

SUBMITTER: Adelman K 

PROVIDER: S-EPMC2775335 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature