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Repression of MHC class II gene transcription in trophoblast cells by novel single‐stranded DNA binding proteins
Author(s) -
Murphy Shawn P.,
Gollnick Sandra O.,
Pazmany Tamas,
Maier Patricia,
Elkin Galina,
Tomasi Thomas B.
Publication year - 1997
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/(sici)1098-2795(199708)47:4<390::aid-mrd5>3.0.co;2-f
Subject(s) - biology , trophoblast , microbiology and biotechnology , enhancer , major histocompatibility complex , response element , promoter , transcription factor , gene , gene expression , placenta , genetics , fetus , pregnancy
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 (IAαNRE) in the promoter of the mouse class II gene IAα that represses IAα transcription in trophoblast cells. IAαNRE, 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 IAαNRE binding proteins (IAαNRE BPs) are conserved in species with hemochordial placentas, and suggest that IAαNRE binding activity is restricted primarily to trophoblast cells. Interestingly, the IAαNRE BPs bind to the IAαNRE antisense strand in a sequence‐specific manner. IAαNRE represses transcription from the IAα 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. Mol. Reprod. Dev. 47:390–403, 1997. © 1997 Wiley‐Liss, Inc.