An enhancer located in a CpG-island 3' to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter.
The gene encoding the CD3-epsilon chain of the T cell receptor (TCR/CD3) complex is uniquely transcribed in all T lymphocyte lineage cells. The human CD3-epsilon gene, when introduced into the mouse germ line, was expressed in correct tissue-specific fashion. The gene was then screened for T lymphocyte-specific cis-acting elements in transient chloramphenicol transferase assays. The promoter (-228 to +100) functioned irrespective of cell type. A 1225 bp enhancer with strict T cell-specificity was found in a DNase I hypersensitive site downstream of the last exon, 12 kb from the promoter. This site was present in T cells only. The CD3-epsilon enhancer did not display sequence similarity with the T cell-specific enhancer of CD3-delta, a related gene co-regulated with CD3-epsilon during intrathymic differentiation. The CD3-epsilon enhancer was unusual in that it constituted a CpG island, and was hypomethylated independent of tissue type. Two HTLV I-transformed T cell lines were identified in which the CD3-epsilon gene was not expressed, and in which the enhancer was inactive.
Clevers
H
H
Dana-Farber Cancer Institute, Boston, MA 02115.
Lonberg
N
N
Dunlap
S
S
Lacy
E
E
Terhorst
C
C
D000818:Animals; D001483:Base Sequence; D015500:Chloramphenicol O-Acetyltransferase; D004252:DNA Mutational Analysis; D003850:Deoxyribonuclease I; D004742:Enhancer Elements, Genetic; D005091:Exons; D006801:Humans; D008745:Methylation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000378:metabolism*
D011948:Receptors, Antigen, T-Cell; C061836:antigen T cell receptor, epsilon chain; D015500:Chloramphenicol O-Acetyltransferase; D003850:Deoxyribonuclease I