Active repression of major histocompatibility complex class I genes in a human neuroblastoma cell line.
Human neuronal cells express neither major histocompatibility complex (MHC) class I RNA nor cell surface molecules but can be induced to do so by various cytokines. In the present studies, we report that expression of MHC class I in a neuroblastoma cell line, CHP-126, is actively repressed. This repression is mediated by the combined effects of a series of upstream silencer elements. Removal of the silencers reveals not only an active promoter element but also the presence of an active enhancer. Four silencers have been identified and shown to have distinct sequences, binding factors, and patterns of function. One element is located between -724 and -697 base pairs (bp) and corresponds to a silencer involved in tissue-specific regulation of class I gene expression. Three additional elements occur between -503 and -402 bp. One of these corresponds to a c-jun responsive element. Neither of the remaining elements corresponds to DNA sequences known to regulate expression of other genes. These data demonstrate that MHC class I expression normally is actively repressed in neuronal cells and suggest a model of rapid and specific triggering of class I in neuronal cells in response to infection.
Murphy
C
C
Experimental Immunology Branch, DBS, NCI, National Institutes of Health, Bethesda, Maryland 20892-1360, USA.
Nikodem
D
D
Howcroft
K
K
Weissman
J D
JD
Singer
D S
DS
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D012097:Repressor Proteins