A T cell-specific enhancer is located in a DNase I-hypersensitive area at the 3' end of the CD3-delta gene.
During intrathymic differentiation, the genes coding for the T cell receptor/CD3 (TCR/CD3) complex are expressed in stages resulting in surface expression of competent receptors on the most mature T cells. The CD3-delta, gamma and epsilon proteins, which are expressed intracellularly in the earliest detectable cells of T lineage, form the core of the TCR/CD3 complex. In the present investigation aimed at understanding the tissue specific expression of the murine CD3-delta gene, a T cell specific DNase I hypersensitive site was found 0.6 kb downstream of the polyadenylation site of the gene. A 0.4 kb genomic fragment encompassing this hypersensitive site exhibited properties of a strictly T cell-specific transcriptional enhancer which acts in a position- and orientation-independent manner. However, the activity of the promoter region was not found to be T cell restricted. Within this novel T cell-specific enhancer region, sequence motifs were found which are shared with the promoters of both the mouse and human CD3-delta genes; in this region we also found sequence homologies to the enhancer core element of the thymotropic viruses SL3 and RadLV. These findings suggest that regulatory elements 3' of the CD3-delta gene are at least in part responsible for its exclusive expression in thymus-derived lymphocytes.
Georgopoulos
K
K
Dana-Farber Cancer Institute, Laboratory of Molecular Immunology, Boston, MA 02115.
van den Elsen
P
P
Bier
E
E
Maxam
A
A
Terhorst
C
C
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D002460:Cell Line; D004247:DNA / Q000032:analysis / Q000235:genetics; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D006825:Hybridomas; D008969:Molecular Sequence Data; D009101:Multiple Myeloma; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013945:Thymoma; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000945:Antigens, Differentiation, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D004247:DNA; D004262:DNA Restriction Enzymes; D003850:Deoxyribonuclease I