Class I MHC genes encoding transplantation antigens are ubiquitously expressed, although their level of expression varies among the tissues, reflecting regulated expression of the genes. Analysis of the 5' flanking DNA sequences of a swine class I gene has demonstrated that in addition to the promoter, this region contains a series of negative and positive regulatory elements. Each of these elements functions through its binding of specific trans acting factors. One of the silencer elements associated with this gene consists of a regulatory DNA complex in which reside overlapping negative and positive elements. Analysis of this complex has led to the proposal that class I genes are negatively regulated and that tissue-specific levels of gene expression result from an equilibrium between the activities of the negative and positive elements associated with the complex.