An enhancer located in a CpG-island 3' to the TCR-CD3-ε gene confers T lymphocyte-specificity to its promoter

Abstract

The gene encoding the CD3-ε chain of the T cell receptor (TCR/CD3) complex is uniquely transcribed in all T lymphocyte lineage cells. The human CD3-ε 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-ε enhancer did not display sequence similarity with the T cell-specific enhancer of CD3-δ, a related gene co-regulated with CD3-ε during intrathymic differentiation. The CD3-ε 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-ε gene was not expressed, and in which the enhancer was inactive.