HLA-G unique promoter region: functional implications.
In contrast to the highly polymorphic HLA class Ia genes that exhibit a broad somatic tissue distribution, the restricted constitutive expression of HLA-G to trophoblast and a subset of thymic epithelial cells suggests tight transcriptional control of this MHC class Ib gene. Transactivation of MHC class I genes is mediated by three major regulatory modules present in their promoter region namely enhancer A, ISRE, and SXY. The 220-bp promoter sequence of HLA-G comprises modified enhancer A and SXY modules and lacks the ISRE which renders this gene unresponsive to NK-kappaB, IRF1, and class II transactivator DNA-binding factors. A number of other HLA-G upstream regulatory elements have recently been described. Using different transgenic HLA-G mouse models under the control of the HLA-G promoter, several groups have shown by in situ hybridization and/or qualitative or quantitative RT-PCR that constitutive HLA-G transcriptional expression in placental tissue decreased with gestational time. This suggests that once the placenta is fully formed, the functions of HLA-G might not be so crucial.
Solier
C
C
INSERM U395, CHU Purpan, BP3028, 31024 Toulouse Cedex 3, France.
Mallet
V
V
Lenfant
F
F
Bertrand
A
A
Huchenq
A
A
Le Bouteiller
P
P
D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D016328:NF-kappa B; D007372:Interferons