Potential regulatory sequences in the untranslated regions of the baboon MHC class Ib gene, Paan-AG, more closely resemble those in the human MHC class Ia genes than those in the class Ib gene, HLA-G

Abstract

The baboon major histocompatibility complex (MHC) class Ib gene, Paan-AG, is structurally similar to the human MHC class Ia gene, HLA-A, but exhibits characteristics similar to those of the class Ib gene HLA-G. These include limited polymorphism, alternative splicing of a single message, and restricted tissue distribution, with high expression in the placenta. In order to determine whether regulatory elements controlling expression of Paan-AG resemble those of HLA-A or HLA-G, we cloned the 5' and 3' untranslated regions of Paan-AG. Unexpectedly, sequence comparisons showed that potential regulatory elements in Paan-AG strikingly resembled those in HLA-A and differed in major respects from those in HLA-G. Unlike HLA-G, Paan-AG contained an intact interferon-gamma stimulated response element (ISRE) in the promoter. Studies using luciferase reporter assays showed that the Paan-AG ISRE was functional. The basal activity of the Paan-AG ISRE and its response to interferon-gamma was similar to that of class Ia MHC genes. Further, we identified an ISRE in the 3' untranslated region of Paan-AG that is known to be functional in HLA-A2 but is deleted in HLA-G. These experiments predict that functional studies may demonstrate differences in regulation of expression of Paan-AG and HLA-G genes, which could restrict the use of the baboon as a primate model for studying HLA-G expression and function.

Comparative Genetics of MHC Polymorphisms in Different Primate Species: Duplications and Deletions

“…This gene also has a premature stop codon and possesses an expression profile similar to that of HLA-G [40]. An equivalent has recently been described for baboons [41], suggesting that this is common to the Old World monkey lineage. Most New World monkeys examined thus far appear to lack the functional equivalents of HLA-A, -B, and -C [42].…”

Transcriptional and Posttranscriptional Regulations of theHLA-GGene

“…These variable sites may be important for the regulation of HLA-G expression and may act in different ways. Polymorphisms in the proximal promoter of Paan-AG , the functional homologue of HLA-G in the Olive Baboon, have been shown to influence NF- κ B binding and transcription activity [82, 83]. However, the human variable sites may act by mechanisms differing from those described above because, generally, these variable sites do not coincide with known regulatory elements (Figure 1).…”

The role of HLA-G in human pregnancy

“…We cloned the 5' and 3' untranslated regions of Paan-AG and compared it to other human MHC class I genes. Sequence comparisons showed that potential regulatory elements in Paan-AG strikingly resembled those in class Ia and differed in major respects from those in HLA-G [51]. Unlike HLA-G , which contains a partially deleted and non-functional interferon-γ stimulated response element (ISRE), Paan-AG contained an intact ISRE in the promoter.…”

“…Unlike HLA-G , which contains a partially deleted and non-functional interferon-γ stimulated response element (ISRE), Paan-AG contained an intact ISRE in the promoter. Furthermore, studies using luciferase reporter assays showed that the Paan-AG ISRE was functional [51]. Basal activity of Paan-AG ISRE and response to interferon-γ was similar to that of class Ia MHC genes.…”