Positive selection induces CD4 promoter and enhancer function.
Developmental expression of the CD4 gene in mature T cells is controlled by at least four transcriptional control elements: a promoter, two enhancers and a silencer. In this report we use a transgenic approach to study the mechanisms in which these elements interact to convey appropriate tissue- and cell-specific expression at all stages of T cell development. Our data indicate that the control of CD4 gene expression requires the interaction of multiple elements functioning in different combinations at different stages of T cell development. Expression of the CD4 gene in immature CD4+CD8+ thymocytes requires a third enhancer element located in the 3' flanking region of the CD4 gene. Interestingly, the CD4 promoter and proximal/distal enhancers first begin to function at the HSAlo CD69lo H-2Khi CD4 single-positive stage; cells of this phenotype are believed to have survived positive selection. These data indicate that the CD4 promoter and late enhancer elements are induced by positive selection; thus, the final maturation process is an active event that requires the initiation of a novel program of gene expression.
Adlam
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M
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Duncan
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Ng
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Siu
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D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic / Q000276:immunology; D019076:Transgenes / Q000276:immunology
D015704:CD4 Antigens