We have introduced a human Pglobin minilocus, containing the recently described dominant control region (DCR), the Pglobln or Thy-l gene, and a thymidine kinase (tk)-neos gene into erythroid and nonerythroid cells. Analysis of the transcription levels of the genes shows that the DCR directs high levels of human f3-globin, Thy-l and tk-neo expression independent of Integration sites in an erythrold-specific manner. The presence of the DNAasel hypersensitive sites at the Send of the locus is required for this effect on the homologous and heterologous gene. An analysis of the DCR chromatin in transfected mouse erythroleukemic cells suggests that the formation of the hypersensitive sites in this region precedes fl-globin gene expression.