A spectrum of gene regulatory phenomena at mammalian beta-globin gene loci

Abstract

The beta-globin gene cluster in mammals, consisting of a set of erythroid-specific, developmentally activated, and (or) silenced genes, has long presented a model system for the investigation of gene regulation. As the number and complexity of models of gene activation and repression have expanded, so too has the complexity of phenomena associated with the regulation of the beta-globin genes. Models for expression from within the locus must account for local (promoter-proximal), distal (enhancer-mediated), and domain-wide components of the regulatory pathways that proceed through mammalian development and erythroid differentiation. In this review, we provide an overview of transcriptional activation, silencing, chromatin structure, and the function of distal regulatory elements involved in the normal developmental regulation of beta-globin gene expression.