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 expres sion of MHC class I in a neuroblastoma cell line, CHP-126, is actively repressed. This repression is mediated by the combined effects of a s eries 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 disti nct 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 expres sion. Three additional elements occur between -503 and -402 bp, One of these corresponds to a c-jun, responsive element. Neither of the rema ining elements corresponds to DNA sequences known to regulate expressi on of other genes, These data demonstrate that MHC class I expression normally is actively repressed in neuronal cells and suggest a model o f rapid and specific triggering of class I in neuronal cells in respon se to infection.