Tissue-specific nuclear factors mediate expression of the CD3 delta gene during T cell development.
An obligatory step towards T cell maturation is expression of the CD3 gene products which occurs very early during thymic differentiation and may even precede migration to the thymus. Delineation of the transcriptional mechanisms that determine expression of the CD3 complex in immature and mature T cells will help us understand the molecular events that govern T cell development. We have previously reported that a 400 bp region 3' of the CD3 delta gene functions as a transcriptional enhancer with strong specificity for T cells. Here we identify two elements in the CD3 delta enhancer which mediate its T cell restricted function. Element delta A can function as an independent enhancer while element delta B has no independent function but augments the activity of element delta A. Together, delta A and delta B are sufficient to reconstitute the activity of the CD3 delta enhancer. Nucleoprotein complexes found in mature T cells have been identified whose presence correlates with activity of these two elements. Since these protein binding sites are conserved in other genes of the TCR-CD3 complex, elements delta A and delta B and their cognate nuclear factors may play an important role in T cell development.
Georgopoulos
K
K
Laboratory of Molecular Immunology, Dana Farber Cancer Institute, Harvard Medical School, MA.
Galson
D
D
Terhorst
C
C
D015703:Antigens, CD / Q000235:genetics*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D017252:CD3 Complex; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D013945:Thymoma; D013953:Thymus Neoplasms; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D004247:DNA