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Regulation of the Expression of Class II Genes of the Human Major Histocompatibility Complex in Tumor Cells a
Author(s) -
GAMBARI ROBERTO,
BARBIERI RAFAELLA,
PIVA ROBERTA,
TECCE RAFFAELE,
FISHER PAUL B.,
GIACOMINI PATRIZIO,
NATALI PIER GIORGIO
Publication year - 1987
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1987.tb36258.x
Subject(s) - biology , major histocompatibility complex , demethylating agent , human leukocyte antigen , gene , microbiology and biotechnology , mhc class i , cd74 , dna methylation , transcription (linguistics) , genetics , gene expression , antigen , linguistics , philosophy
The control of expression of human class II MHC genes has been studied in lymphoid and melanoma cells. Specific unmethylation of all restriction sites nearby the promoter regions has been detected in all cell lines and tissues studied, irrespective of their ability to express class II MHC products. The main functional role of DNA methylation appears, on the contrary, to be the regulation of a fraction of the nucleotide polymorphism of class II MHC genes. Constitutive expression of these genes can be modified by recombinant IFN-gamma and by the demethylating agent 5-azacytidine. Both the modifiers differentially regulate the levels of class II MHC and invariant chain products. In melanoma cells IFN-gamma derepresses transcription of a 1.2-Kb HLA-DR alpha mRNA, but does not affect the levels of a 0.8-Kb HLA-DR alpha specific mRNA. These molecular changes are triggered by IFN-gamma through a protein-synthesis-dependent pathway.