Locus control regions: coming of age at a decade plus

The beta-globin locus control region (LCR) is the founding member of a novel class of cis-acting regulatory elements that confer high level, tissue-specific, site-of-integration-independent, copy number-dependent expression on linked transgenes located in ectopic chromatin sites. Knowledge from beta-globin and other LCR studies has shed light on our understanding of the long-range interaction between enhancers and promoters, the relationship between chromatin conformation and transcriptional regulation, and the developmental regulation of multiple gene loci. After over a decade of investigation and discovery, we take a retrospective look at the beta-globin LCR and other LCRs, summarize their properties and review models of LCR function.