DEVELOPMENTAL REGULATION OF THE HUMAN BETA-GLOBIN CLUSTER

Expression of the genes of the human beta-globin cluster is subject to stringent developmental regulation. An integral component of this con trol is competition between the gamma- and beta-promoters for the upst ream regulatory sequences of the Locus Control Region (LCR). We have d efined two stage selector elements (SSE end SSE-2) located in the prox imal gamma-promoter and gamma-gene 5'UTR which mediate rile preferenti al interaction of the gamma-gene with the LCR in the foetal developmen tal stage. The activity of both elements is dependent upon the binding of foetal and erythroid-specific proteins. We have purified the prote in binding the proximal SSE and characterised it as a complex between rite ubiquitous transcription factor CP2 and a 40 KD partner protein. Comparative studies between human CP2 and the chicken stage selector p rotein, NF-E4, demonstrate homology between the protein complexes. The se findings demonstrate that competitive silencing of globin globin ge nes mediated by developmentally-specific protein complexes is conserve d in evolution.