T Cell-specific Expression of the MurineCD3δ Promoter

Hong-bin Ji, Anita Gupta, Susumu Okamoto, Michael D. Blum, Lujian Tan, Mary B. Goldring, Elizabeth Lacy, Ananda L. Roy, Cox Terhorst
2002 Journal of Biological Chemistry  
T cell-specific expression of human and mouse CD3␦ is known to be governed by an enhancer element immediately downstream from the gene. Here we demonstrate by transgenic and in vitro studies that the murine CD3␦ (mCD3␦) promoter prefers to be expressed in cells of the T lineage. Deletion analyses of a promoter segment (؊401/؉48 bp) followed by transient transfections indicate that upstream elements between ؊149 and ؊112 bp contribute to full expression of the gene. Furthermore, a core promoter
more » ... e, a core promoter region ؊37/؉29 appears to contribute to a T cell specificity. Using substitution mutant scanning, four positive and one negative regulatory elements were found within the mCD3␦ core promoter. The first two positive elements comprise two classical initiator-like sites, which recruit TFII-I, whereas a third contains a functional Ets binding site. Immediately adjacent to the observed transcription start site is a negative element that utilizes the transcription regulator YY1. The last positive regulatory element contains a potentially functional CREB binding site and the minor transcriptional start site. Because NERF-2, Elf-1, and Ets-1 are expressed preferentially in lymphocytes and because, in addition, YY1 represses the promoter activity strongly in non-T cells, we conclude that the combination of these transcription factors contributes to the T cell-specific expression pattern of mouse CD3␦.
doi:10.1074/jbc.m201025200 pmid:12324448 fatcat:sh7nvnjwvnccheshhcclefdkcq