Cis-acting sequences regulating expression of the human α-globin cluster lie within constitutively open chromatin

Abstract Current models suggest that tissue-specific genes are arranged in discrete, independently controlled segments of chromatin referred to as regulatory domains. Transition from a closed to open chromatin structure may be an important step in the regulation of gene expression. To determine whether the human α-globin cluster, like the β-globin cluster, lies within a discrete, erythroid-specific domain, we have examined the long-range genomic organization and chromatin structure around this region. The α genes lie adjacent to at least four widely expressed genes. The major α-globin regulatory element lies 40 kb away from the cluster within an intron of one of these genes. Therefore, unlike the β cluster, cis-acting sequences controlling α gene expression are dispersed within a region of chromatin that is open in both erythroid and nonerythroid cells. This implies a difference in the hierarchical control of α- and β-globin expression.