The regulatory network controlling beta-globin gene switching.

The human globin gene cluster, which represents a prototypical eukaryotic multigene locus, has been investigated for more than two decades and is classic model for coordinate control of tissue-specific gene expression. It is well known that globin gene expression is restricted to specific tissues and that globin genes are sequentially switched on during development. What intricate regulatory mechanisms account for tissue-specific transcriptional control of globin gene expression? Previous studies have focused on the interactions of trans-acting factors and cis-acting elements including the locus control region (LCR), which is considered a potent enhancer in globin gene switching. More recent studies have not only focused on the local DNA regulatory elements but also on remodelling of chromatin and transcription at the globin gene cluster within the native genomic context. Moreover, several studies have presented extensive data that address whether the LCR is required to open the chromatin. Although there is increased insight into the regulation of the beta-globin gene switching, many aspects relating to the developmental activation of distinct globin genes remain elusive.