Promoter analysis of the murine T-cell protein tyrosine phosphatase gene

The T-cell protein tyrosine phosphatase (TC PTP) is expressed ubiquitously at all stages of mammalian development. However, mRNA levels fluctuate in a cell-cycle-dependent manner, reaching peak levels in late G1, and rapidly decreasing in S phase. Furthermore, TC PTP being present in higher amounts in lymphoid tissues, we have recently shown that it is essential for proper maintenance of both the bone marrow micro-environment and B- and T-cell fu nctions. In order to better understand the elements controlling the express ion pattern of this gene, we have isolated and characterized approx. 4 kb o f the murine TC PTP promoter. DNA sequencing of the proximal 5' region reve aled the absence of both TATAA and CAAT boxes. Primer extension analysis an d SI nuclease mapping techniques identified multiple transcription initiati on sites. Functional promoter activity was determined using transfection ex periments of promoter deletion constructs fused to a CAT reporter construct . Our results indicate that the minimal promoter sequence required for func tional expression is contained within the first 147 bp of the TC PTP promot er. In addition, consistent with the cell-cycle-dependent expression of TC PTP, we localized a domain between 492 and 1976 bp from the transcription i nitiation site through which repression occurs. In conclusion, although ini tiator-driven transcription allows for ubiquitous expression of TC PTP, we define general transcription motifs present within the promoter that may me diate specific modulations of the TC PTP gene. (C) 1999 Elsevier Science B. V. All rights reserved.