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Originally published In Press as doi:10.1074/jbc.M201025200 on September 24, 2002

J. Biol. Chem., Vol. 277, Issue 49, 47898-47906, December 6, 2002
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T Cell-specific Expression of the Murine CD3delta Promoter*

Hong-bin JiDagger §, Anita GuptaDagger , Susumu OkamotoDagger , Michael D. Blum||, Lujian Tan**Dagger Dagger , Mary B. Goldring**Dagger Dagger , Elizabeth Lacy||, Ananda L. Roy§§, and Cox TerhorstDagger

From the Divisions of Dagger  Immunology and ** Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, the Dagger Dagger  New England Baptist Bone and Joint Institute, Harvard Institutes of Medicine, Boston, Massachusetts 02115, the || Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, Weill Graduate School of Medical Sciences of Cornell University, New York 10021, and the §§ Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111

T cell-specific expression of human and mouse CD3delta 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 CD3delta (mCD3delta ) 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 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 mCD3delta 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 CD3delta .

* This work was supported in part by National Institutes of Health Grants AI-17651 (to C. T.), AI-45150 (to A. L. R.), and AR-45378 (to M. B. G).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Division of Immunology, RE-206, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215. E-mail: hji@caregroup.harvard.edu.

Recipient of a fellowship from the Crohn's and Colitis Foundation Association.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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