Specific binding of nuclear factors to the HLA-G gene promoter correlates with a lack of HLA-G transcripts in first trimester human fetal liver.
The nonclassical MHC class I HLA-G antigen is expressed in cytotrophoblasts during pregnancy and may play a role in inhibiting lysis by maternal natural killer cells. HLA-G gene transcription was analyzed in human fetal liver of 6-8 wk of gestation, a development stage where classical HLA class I expression is very reduced. We demonstrated that HLA-G transcription is undetectable in these cells and we investigated the molecular mechanisms that control the lack of HLA-G gene transcription. We compared protein interactions of nuclear extracts from first trimester fetal livers, YT2C2-PR (HLA-G negative) and JEG-3 (HLA-G positive) cell lines to a 244-bp EcoR I/Hind III DNA region located 1.2 kb from the HLA-G gene, previously shown to direct HLA-G expression in transgenic mouse placenta. A strong specific C7-factor was specifically detected in first trimester fetal liver that could account for the inhibition of HLA-G transcription. Interaction of C7-factor and cell-specific factors previously detected in YT2C2 cell line (C5, C6) with two distinct regulatory regions identify this 244-bp EcoR I/Hind III fragment as a putative target for inhibition of HLA-G transcription.
Moreau
P
P
CEA, Service de Recherches en Hémato-immunologie, DSV, DRM, Centre Hayem, Hôpital Saint-Louis, Paris, France. moreau@dsvidf.cea.fr
Lefebvre
S
S
Gourand
L
L
Dausset
J
J
Carosella
E D
ED
Paul
P
P
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000032:analysis; D005260:Female; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011262:Pregnancy Trimester, Second; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D009687:Nuclear Proteins; D004247:DNA