An enhancer located in a CpG-island 3′ to the TCR/CD3-epsilon gene confers T lymphocyte-specificity to its promoter.

Abstract

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.