The mammalian globin gene clusters provide a paradigm for studying the relationship between genome structure and function. As blood stem cells undergo lineage specification and differentiation to form red blood cells, the chromatin structure and expression of the α-globin cluster change. The gradual activation of the α-globin genes in well-defined cell populations has enabled investigation of the structural and functional roles of its enhancers, promoters and boundary elements. Recent studies of gene regulatory processes involving these elements at the mouse α-globin cluster have brought new insights into the general principles underlying the three-dimensional structure of the genome and its relationship to gene expression throughout time.
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