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MHC class I gene expression is negatively regulated by the proto‐oncogene, c‐jun.
Author(s) -
Howcroft T.K.,
Richardson J.C.,
Singer D.S.
Publication year - 1993
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1993.tb05985.x
Subject(s) - biology , gene expression , gene , genetics , oncogene , mhc class i , major histocompatibility complex , regulation of gene expression , expression (computer science) , microbiology and biotechnology , cell cycle , computer science , programming language
The trans‐acting factor AP‐1 is a heterodimeric complex composed of c‐Jun and c‐Fos family proteins which bind and regulate genes containing a TPA responsive enhancer element. Although AP‐1 binding sites have been identified within the regulatory region of major histocompatibility complex (MHC) class I genes in vitro, the role of AP‐1 in regulating MHC class I transcription in vivo has not been investigated previously. The present study demonstrates that expression of c‐Jun results in decreased MHC class I promoter activity as determined in cotransfection assays of an MHC class I reporter construct with a c‐Jun expression construct. The c‐Jun responsive element is located between bp −440 and −431 upstream of initiation of transcription as determined both functionally and by direct binding of purified c‐Jun. Furthermore, over‐expression of c‐Jun reduced the steady state levels of endogenous MHC class I RNA in murine L cells by approximately 10‐fold. These data indicate that c‐Jun/AP‐1 acts as a negative trans‐acting factor that down‐regulates MHC class I gene expression.