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 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.
Jane
S M
SM
Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Parkville, Vic.
Amrolia
P
P
Cunningham
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D004220:Disulfides / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D006825:Hybridomas / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007075:Immunoglobulin M / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D011233:Precipitin Tests; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation
D000911:Antibodies, Monoclonal; D004220:Disulfides; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M