Cluster specific regulation pattern of upstream regulatory elements in human alpha- and beta-globin gene clusters.

Located in different chromatin contexts and with different developmental switching mode, human alpha- and beta-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 alpha-upstream regulatory element (alpha-URE) and beta-locus control region (beta-LCR). The results showed that, after exchange, the developmental switching modes of human alpha- and beta-like globin genes had changed, with lost expression of epsilon- and alpha1-genes. Their expression levels also decreased. Our study suggests that the regulation of alpha-URE and beta-LCR on the expression level and developmental switching mode of downstream globin genes is cluster specific.