Regulation of lrp gene expression by H-NS and Lrp proteins in Escherichia coli: dominant negative mutations in lrp.

Lrp (leucine-responsive regulatory protein) is a global transcription factor of Escherichia coli and regulates, negatively or positively, many genes including lysU, which encodes lysyl-tRNA synthetase. Dominant negative mutations that derepress lysU expression were isolated in this study. These mutations affected a predicted DNA-binding domain of Lrp and mutants were defective DNA-binding domain of Lrp and mutants were defective both in activation of ilvIH expression and in repression of lysU expression. Consistent with the previous notion that lrp is autoregulated, lrp expression was derepressed by these mutations and repressed by multi-copy plasmids carrying lrp+. Moreover, we found by gene fusion and Northern blot hybridization that the "histone-like" protein, H-NS, bound specifically to a promoter segment of lrp in vitro, and the level of lrp expression increased in the hns null mutant. These results indicated that the lrp gene is not only feedback regulated by Lrp but is also controlled by H-NS protein.