DNASE I HYPERSENSITIVITY MAPPING AND PROMOTER POLYMORPHISM ANALYSIS OF HUMAN C4

Human complement component C4 is encoded by two structurally distinct loci in the major histocompatibility complex (MHC) class III region. T he two isotypes, C4A and C4B, differ at only four residues in the C4d fragment, but C4 constitutes the most polymorphic of the complement co mponents. It is not known, however, whether the regions involved in th e regulation of C4 expression also display polymorphic variation. By u sing the technique of DNase I hypersensitivity mapping, we established that the only area of transcriptional activity for C4 in the hepatocy te cell Line, HepG2, occurs approximatly 500 base pairs upstream of th e transcriptional start site. This region was found to be remarkably c onstant in sequence when analyzed in the context of differing MHC hapl otypes including HLA B57, C4A6, C4B1, DR7, which has been correlated w ith reduced expression of the C4A isotpye. Similarly, polymerase chain reaction followed by single-strand conformation polymorphism analysis failed to demonstrate any promoter polymorphisms in 103 individuals c omprising 52 systemic lupus erythematosus patients and 51 healthy cont rols.