Studies of the H60a locus in C57BL/6 and 129/Sv mouse strains identify the H60a 3′UTR as a regulator of H60a expression

The minor histocompatibility antigen 60 (H60a) is expressed in BALB/C and 129/Sv but not in C57BL/6 strains of mice. We recently found that IFNγ down-regulates H60a, but the mechanism of regulation is not known. To better understand the regulation of H60a, we examined the genomic locus of H60a in 129/Sv and C57BL/6 strains. We found that the upstream regulatory region of H60a was present and functional in both strains. Interestingly, IFNγ can down-regulate H60a transcripts in cell lines from 129/Sv but not C57BL/6 strains of mice, suggesting that IFNγ-dependent regulation of H60a proceeds through cis elements other than the conserved promoter region. We determined that the regulation of H60a by IFNγ proceeds through the 3′UTR of H60a, which is present in 129/Sv, but not C57BL/6 cells. We also found that the H60a 3′UTR and microRNAs can contribute to the level of constitutive expression of H60a in tumor cell lines. We conclude that in 129/Sv strain mice, H60a can be regulated by its 3′UTR through IFNγ and unknown microRNAs. Since H60a mediates NK cell target recognition, our studies identify a cis element that can regulate virus and tumor surveillance.