Saccharomyces cerevisiae ire15 mutant has a defect in the expression of INO1, showing the inositol auxotrophic phenotype [Nikawa, J. (1994) Gene 149, 367-372]. We have isolated five yeast genes which suppress the ire15 mutation in multiple copies by genetic complementation. Among them, one gene, designated as SCS2, also suppressed the choline-sensitive dominant mutation, CSE1 [Hosaka, K. et al. (1992) J. Biochem. 111, 352-358]. The CSE1 mutation is not allelic to ire15. Sequencing analysis revealed that the SCS2 gene encodes 244 amino acid residues with a calculated molecular mass of 26,866. INO2/SCS1, which is another suppressor gene for CSE1 and is known to be a positive factor for INO1 expression, also suppressed the growth defect of the ire15 mutant. These results clearly indicate that the ire15 and CSE1 mutations genetically interact and the SCS2 and INO2/SCS1 genes are involved in the regulation of INO1 expression.