Evidence for a locus activation region: the formation of developmentally stable hypersensitive sites in globin-expressing hybrids

Abstract

We have analyzed the chromatin structure of the human β - globin locus in somatic cell hybrids resulting from the fusion of human non-erythroid cells and mouse erythroleukemia (MEL) cells. In these hybrids, the human adult β-globin gene, but neither the embryonic nor fetal globin genes, is activated transcriptionally. In addition, the DNase I-resistant β-like globin locus characteristic of the parental non-erythroid human cells (1,2) is reorganized over an approximately 80 kb region, including the formation of the developmentally stable hypersensitive sites 50 kb 5′ and 20 kb 3′ of the activated adult β-globin gene (2,3). These results are consistent with the hypothesis that events occurring at the 5′ and/or 37′ developmentally stable hypersensitive sites are important, if not necessary, for the activation of the β-globin locus.