REPRESSION OF MHC CLASS-II GENE-TRANSCRIPTION IN TROPHOBLAST CELLS BYNOVEL SINGLE-STRANDED-DNA BINDING-PROTEINS

The maintenance of the fetus during pregnancy has been attributed to t he absence of major histocompatibility complex (MHC) class II antigens on fetal trophoblastic cells that make contact with the maternal immu ne system. However, the mechanism(s) by which class II genes are regul ated in trophoblast cells is unclear. We have identified a negative re gulatory element (IA alpha NRE) in the promoter of the mouse class II gene IA alpha that represses IA alpha transcription in trophoblast cel ls. IA alpha NRE, located from -839 to -828, binds transacting factors from rat, mouse and human trophoblast cells, but not from 18 other ce ll lines tested. These results indicate that IA alpha NRE binding prot eins (IA alpha NRE BPs) are conserved in species with hemochordial pla centas, and suggest that IA alpha NRE binding activity is restricted p rimarily to trophoblast cells. Interestingly, the IA alpha NRE BPs bin d to the IA alpha NRE antisense strand in a sequence-specific manner. IA alpha NRE represses transcription from the IA alpha promoter in a p osition-dependent manner, and has a minor down-regulatory effect on th e activity of the SV40 promoter/enhancer. Our results demonstrate that MHC class II gene transcription is repressed in fetal trophoblast cel ls by sequence-specific, single-stranded DNA binding proteins, and sug gest a possible mechanism by which the conceptus is protected from imm une rejection during pregnancy. (C) 1997 Wiley-Liss, Inc.