Developmental regulation of the human beta-globin cluster
Jane, S.M.; Amrolia, P.; Cunningham, J.M.
Australian and New Zealand Journal of Medicine 25(6): 865-869
1995
ISSN/ISBN: 0004-8291 PMID: 8770365 Document Number: 454507
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 (L CR). We have defined two stage selector elements (SSE and SSE-2), located in the proximal gamma-promoter and gamma-gene 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 characterized it as a complex between the ubiquitous transcription factor CP2 and a 40 kD 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.