Cluster specific regulation pattern of upstream regulatory elements in human α- and β-globin gene clusters

Located in different chromatin contexts and with different developmental switching mode, human α- and β-globin gene clusters are co-regulated temporally and quantitatively to keep balanced expression. Here, by exchanging their key upstream regulatory elements (UREs) in cluster level, and investigating the expression level of exogenous globin genes in the bacterial artificial chromosome (BAC) mediated transgenic mice, we explored the similarities and differences in the regulatory effects between α-upstream regulatory element (α-URE) and β-locus control region (β-LCR). The results showed that, after exchange, the developmental switching modes of human α- and β-like globin genes had changed, with lost expression of ε- and α1-genes. Their expression levels also decreased. Our study suggests that the regulation of α-URE and β-LCR on the expression level and developmental switching mode of downstream globin genes is cluster specific.