Hierarchical interactions control CD4 gene expression during thymocyte development.
CD4 gene regulation provides an ideal model for understanding the molecular events that drive T cell development. In this paper we use a transgenic approach to identify a CD4 LCR containing a stage-specific thymocyte enhancer (TE) and a region that protects against position effect variegation. Surprisingly, the TE acts indirectly through the previously defined proximal enhancer and is strongly induced upon commitment to the T cell lineage. We also describe a complex series of hierarchical control element interactions that orchestrate CD4 expression throughout thymopoiesis. These data provide a framework for understanding how CD4 gene expression is regulated in response to lineage commitment decisions.
Adlam
Matthew
M
Department of Microbiology, 701 West 168th Street, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. matthew.adlam@mssm.edu
Siu
Gerald
G
D000818:Animals; D015704:CD4 Antigens / Q000235:genetics*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D019901:Locus Control Region; D038041:Lymphopoiesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology
D015704:CD4 Antigens