Altered regulation of MHC class I genes in different tumor cell lines is reflected by distinct sets of DNase I hypersensitive sites.
MHC class I antigens play a crucial role in immunological functions, e.g. transplant and tumor rejection and antigen presentation. Whereas class I antigens are normally expressed on most adult tissues, albeit in varying amounts, embryonic as well as many tumor cells are characterized by the absence of major histocompatibility complex class I antigens on their cell surfaces. In this study the mechanism controlling the lack of class I expression was analyzed at the level of the chromatin structure. Five DNase I hypersensitive sites were determined at the H-2 D-locus of cell lines constitutively expressing class I genes. Two of them (DH1, located at the TATA box/transcription start site, and DH2, located at the enhancer/interferon response sequence) were absent in the fibrosarcoma IC9 in which expression of the silent Dk class I gene was not inducible. DH1 and DH2 remained absent even after fusion with class-I-positive cells. However, transfected Dk genes were expressed in IC9, and both DH1 and DH2, which were probably derived from the transfected gene, became detectable. In tumor cells expressing class I genes only after treatment with IFN-gamma (e.g. the lung carcinoma CMT64.5) or after in vitro differentiation (F9 embryonal carcinoma cells), DH1 and DH2 were already present before induction of class I expression. However, the intensity of the band indicative of DH2 was reduced in undifferentiated and differentiated F9 cells and in untreated CMT cells.
Maschek
U
U
Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg, FRG.
Pülm
W
W
Hämmerling
G J
GJ
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002843:Chromatin / Q000502:physiology; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D007371:Interferon-gamma / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D002843:Chromatin; D007371:Interferon-gamma; D003850:Deoxyribonuclease I