MULTIPLE NUCLEAR FACTORS BIND TO NOVEL POSITIVE AND NEGATIVE REGULATORY ELEMENTS UPSTREAM OF THE HUMAN MHC CLASS-I GENE HLA-A11

Quantitative expression of class I genes varies widely in different ti ssues, during development and in some neoplastic cells. Regulatory DNA sequences controlling levels of transcription of class I genes have b een characterized in the murine and swine promoters. Although some reg ulatory features appear to be retained in humans, most of them are not evolutionary conserved. In this study, we identify novel DNA sequence s and factors which contribute to the regulation of the human HLA-A11 gene. Two activator elements (-155 to -91 and -335 to -206) and one ne gative element (-172 to -156), distinct from those previously describe d are mapped within 335 bp upstream of exon 1 of the human HLA-A11 gen e. Various nuclear factors bind to these regulatory elements, some of which are cell restricted or interact with evolutionary divergent regu latory sequences of the human class I gene promoter. Two of the five D NA-binding sites characterized in this work bind at least two proteins which compete for the occupancy of their site. The identification of these new regulatory elements provides a more comprehensive basis for the understanding of physiological or pathological modulation of MHC c lass I transcription in humans.