C-myc represses transiently transfected HLA class I promoter sequences not locus-specifically.
Overexpression of the c-myc oncogene is frequently accompanied by downregulation of Major Histocompatibility Complex (MHC, HLA in humans) class I antigens. In human melanoma c-myc overexpression downmodulates HLA-B expression, whereas HLA-A is hardly affected. Repression of HLA-B is mediated through the core promoter, containing a CAAT-box and a non-conventional TATA-box. We show evidence that in transient transfection assays the HLA-A2 and HLA-B7 promoters are repressed by c-myc to the same extent. Therefore, other sequences of the HLA-A and HLA-B genes, possibly intron/exon sequences, should contribute to the locus B-specificity of the downregulation. Furthermore, c-myc does not seem to alter binding of protein complexes to the CAAT- or TATA-box of HLA-B7 or HLA-A2 in gel retardation assays. Comparison of promoters repressed by c-myc reveals a weak consensus sequence of the initiator (Inr) element: TCA(+1)YYYNY. The presence of a TCA sequence in the initiator region of the MHC class I promoter makes downregulation by c-myc through the Inr likely. We speculate that the Inr contributes to MHC class I promoter activity by stimulating recruitment of TFIID to the weak, non-conventional TATA-box, thereby making it susceptible to repression by c-myc through the Inr.
Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
M
M
Griffioen
L T
LT
Peltenburg
D A
DA
van Oorschot
P I
PI
Schrier
D001483:Base Sequence; D015536:Down-Regulation / Q000235:genetics* / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D016259:Genes, myc / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000378:metabolism; D015793:HLA-B7 Antigen / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000235:genetics; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000276:immunology*; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D016385:TATA Box / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen