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 cytotrophob lasts during pregnancy and may play a role in inhibiting lysis by mate rnal natural killer cells. HLA-G gene transcription was analyzed in hu man fetal liver of 6-8 wk of gestation, a development stage where clas sical HLA class I expression is very reduced. We demonstrated that HLA -G transcript-ion is undetectable in these cells and we investigated t he molecular mechanisms that control the lack of HLA-G gene transcript ion. We compared protein interactions of nuclear extracts from first t rimester fetal livers, YT2C2-PR (HLA-G negative) and JEG-3 (HLA-G posi tive) 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 t ransgenic mouse placenta. A strong specific C7-factor was specifically detected in first trimester fetal liver that could account for the in hibition of HLA-G transcription. Interaction of C7-factor and cell-spe cific factors previously detected in YT2C2 cell line (C5, C6) with two distinct regulatory regions identify this 244-bp EcoR I/Hind III frag ment as a putative target for inhibition of HLA-G transcription. Human Immunology 59. 751-757 (1998). (C) American Society for Histocompatib ility and Immunogenetics, 1998. Published by Elsevier Science Inc.