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  • Title: Developmental regulation of the human beta-globin cluster.
    Author: Jane SM, Amrolia P, Cunningham JM.
    Journal: Aust N Z J Med; 1995 Dec; 25(6):865-9. PubMed ID: 8770365.
    Abstract:
    Expression of the genes of the human beta-globin cluster is subject to stringent developmental regulation. An integral component of this control is competition between the gamma- and beta-promoters for the upstream regulatory sequences of the Locus Control Region (LCR). We have defined two stage selector elements (SSE and SSE-2), located in the proximal gamma-promoter and gamma-genes 5'UTR which mediate the preferential interaction of the gamma-gene with the LCR in the foetal developmental stage. The activity of both elements is dependent upon the binding of foetal and erythroid-specific proteins. We have purified the protein binding the proximal SSE and characterised it as a complex between the ubiquitous transcription factor CP2 and a 40 hD partner protein. Comparative studies between human CP2 and the chicken stage selector protein, NF-E4, demonstrate homology between the protein complexes. These findings demonstrate that competitive silencing of globin genes mediated by developmentally-specific protein complexes is conserved in evolution.
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