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Altered regulation of MHC class I genes in different tumor cell lines is reflected by distinct sets of DNase I hypersensitive sites.
Author(s) -
Maschek U.,
Pülm W.,
Hämmerling G.J.
Publication year - 1989
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.1460-2075.1989.tb08356.x
Subject(s) - biology , microbiology and biotechnology , major histocompatibility complex , transfection , cell culture , antigen , genetics
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.