Erythroid-specific nuclease-hypersensitive sites flanking the human β-globin domain

Recent evidence suggests that DNA sequences from the region lying 5′ of the human ε-globin gene are important for erythroid-specific expression of human β-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the β-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the ε-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of ε-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.