Role of ArgP (IciA) in Lysine-Mediated Repression in Escherichia coli

Abstract

ABSTRACT Initially identified as an inhibitor of oriC -initiated DNA replication in vitro , the ArgP or IciA protein of Escherichia coli has subsequently been described as a nucleoid-associated protein and also as a transcriptional regulator of genes involved in DNA replication ( dnaA and nrdA ) and amino acid metabolism ( argO , dapB , and gdhA [the last in Klebsiella pneumoniae ]). ArgP mediates lysine (Lys) repression of argO , dapB , and gdhA in vivo , for which two alternative mechanisms have been identified: at the dapB and gdhA regulatory regions, ArgP binding is reduced upon the addition of Lys, whereas at argO , RNA polymerase is trapped at the step of promoter clearance by Lys-bound ArgP. In this study, we have examined promoter- lac fusions in strains that were argP + or Δ argP or that were carrying dominant argP mutations in order to identify several new genes that are ArgP-regulated in vivo , including lysP , lysC , lysA , dapD , and asd (in addition to argO , dapB , and gdhA ). All were repressed upon Lys supplementation, and in vitro studies demonstrated that ArgP binds to the corresponding regulatory regions in a Lys-sensitive manner (with the exception of argO , whose binding to ArgP was Lys insensitive). Neither dnaA nor nrdA was ArgP regulated in vivo , although their regulatory regions exhibited low-affinity binding to ArgP. Our results suggest that ArgP is a transcriptional regulator for Lys repression of genes in E. coli but that it is noncanonical in that it also exhibits low-affinity binding, without apparent direct regulatory effect, to a number of additional sites in the genome.