Repression of MHC class II gene transcription in trophoblast cells by novel single-stranded DNA binding proteins.

The maintenance of the fetus during pregnancy has been attributed to the absence of major histocompatibility complex (MHC) class II antigens on fetal trophoblastic cells that make contact with the maternal immune system. However, the mechanism(s) by which class II genes are regulated in trophoblast cells is unclear. We have identified a negative regulatory element (IA alpha NRE) in the promoter of the mouse class II gene IA alpha that represses IA alpha transcription in trophoblast cells. IA alpha NRE, located from-839 to -828, binds transacting factors from rat, mouse and human trophoblast cells, but not from 18 other cell lines tested. These results indicate that IA alpha NRE binding proteins (IA alpha NRE BPs) are conserved in species with hemochordial placentas, and suggest that IA alpha NRE binding activity is restricted primarily to trophoblast cells. Interestingly, the IA alpha NRE BPs bind to the IA alpha NRE antisense strand in a sequence-specific manner. IA alpha NRE represses transcription from the IA alpha promoter in a position-dependent manner, and has a minor down-regulatory effect on the activity of the SV40 promoter/enhancer. Our results demonstrate that MHC class II gene transcription is repressed in fetal trophoblast cells by sequence-specific, single-stranded DNA binding proteins, and suggest a possible mechanism by which the conceptus is protected from immune rejection during pregnancy.