Structural characteristics of flavin-containing monooxygenase genes one and two (FMO1 and FMO2).

As a first step in understanding the regulation of the expression of flavin-containing monooxygenases (FMOs), we have isolated the FMO genes from the rabbit and characterized the gene for FMO1. Probes based on the 3', middle and 5' regions of the cDNAs encoding FMO1, FM02, FM03, and FM05 were generated by polymerase chain reaction. A mixture of the 5' probes was used to screen a genomic library, and isolated clones were identified by hybridization with individual 5' probes. The complete gene for FM01 was isolated as three overlapping clones and found to span approximately 40 kb. The gene contains eight introns, ranging in size from 1.4 to 10 kb and nine exons ranging in size from 73 to 747 bases. The gene for FMO1 seems to have multiple transcription start sites. A genomic clone containing a 5' segment of the FM02 gene was isolated and found to contain intron 1, exon 1, and part of intron 2. The first intron of FM02 is considerably smaller than that of FMO1 (0.3 vs. 3.8 kb), and its 3' junction is 52 bases to the 5' of the start codon, compared with 6 bases in the case of FM01. In contrast, the 5' junction of intron 2 is the same distance from the start codon in both genes. The 5'-flanking regions of the FMO1 and FM02 genes contain several putative glucocorticoid responsive elements.