STRUCTURAL CHARACTERISTICS OF FLAVIN-CONTAINING MONOOXYGENASE GENES ONE AND 2 (FMO1 AND FM02)

As a first step in understanding the regulation of the expression of f lavin-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, FMO2, FMO3, and FMO5 were generated by polymerase chain reaction. A mixture of the 5' probes was used to screen a genomic library, and isolated clones w ere identified by hybridization with individual 5' probes. The complet e gene for FMO1 was isolated as three overlapping clones and found to span similar to 40 kb. The gene contains eight introns, ranging in siz e from 1.4 to 10 kb and nine exons ranging in size from 73 to 747 base s. The gene for FMO1 seems to have multiple transcription start sites. A genomic clone containing a 5' segment of the FMO2 gene was isolated and found to contain intron 1, exon 1, and part of intron 2. The firs t intron of FMO2 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, c ompared with 6 bases in the case of FMO1. 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 FMO2 genes contain several put ative glucocorticoid responsive elements.