The on-and-off expression (phase variation)of type 1 fimbriae, encoded by fimA, in Escherichia coli is controlled by the inversion of a promoter-containing 314-basepair DNA element. This element is flanked on each side by a 9-base-pair inverted, repeat sequence and requires closely linked genes for inversion. Homology analysis of the products of these genes, fimB andfimE, reveals a strong similarity with the proposed DNA binding domain of X integrase, which mediates site-specific recombination in the presence of integration host factor. Integration host factor, encoded by himA and hip/himD, binds to the sequence 5' TNYAANNNRTTGAT 3', where Y = pyrimidine and R = purine, in mediating integration-excision. In analyzing the DNA flanking the fim 314-base-pair inversion sequence, we found the adjacent sequence 5' TTTAACTTATTGAT 3', which corresponds perfectly with the consensus integration host factor binding site. To characterize the role of himA in phase variation, we transduced either a deletion of himA or an insertionally inactivated hip/himD gene into an E. coli strain with a fimA-acZ operon fusion. We found the rate of phase variation decreases sharply from 10-3 to <10-5 per cell per generation. Southern hybridization analysis demonstrates that the himA mutation results in a failure of the switch-generated genetic rearrangement. When the transductant was transformed with a himA+ plasmid, normal switching returned. Thus integration host factor is required for normal type 1 runbriae phase variation in E. coli.Genome rearrangement mediated by site-specific recombination is of widespread importance in the control of gene expression in prokaryotes and eukaryotes (1). The molecular basis for the mechanisms has been determined in several systems, including bacteriophage integration-excision (2, 3) and the interrelated invertible DNA elements best exemplified by the flagellar switch in Salmonella (4-6). In both systems the following three sets of factors are required. (i)The cis-specific DNA that acts as the crossing point for the rearrangement.(ii) Site-specific trans-active factors whose genes map near the cis-specific DNA. For example, in X integration the int gene is carried by the bacteriophage (7-9), and in the Salmonella switch the hin gene is located within the invertible DNA (5). (iii) "Host factors" whose genes reside on the bacterial chromosome distant from the site of rearrangement. The best studied host factor is the integration host factor (IHF) of Escherichia coli required for X phage integration (10). IHF consists of two subunits: IHFa, a Mr 10,500 polypeptide encoded by himA that maps at 38 min, and IHF,B, a Mr 9500 polypeptide encoded by hip/himD that maps at 20 min (11)(12)(13)(14). Like Salmonella flagellar expression, type 1 fimbriae of E. coli exhibit phase-variation control. We have shown that E. coli phase variation is transcriptionally regulated (15) and that the oscillating expression is due to the specific inversion of a 314-base-pair (bp) invertible element of DNA that directs transc...