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| DEVELOPMENTAL REGULATION OF LCK GENE-EXPRESSION IN LYMPHOCYTES-T |
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| Author(s): WILDIN RS, GARVIN AM, PAWAR S, LEWIS DB, ABRAHAM KM, FORBUSH KA, ZIEGLER SF, ALLEN JM, PERLMUTTER RM |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 173 Issue: 2 Pages: 383-393 Published: FEB 1 1991 |
| Times Cited: 113 References: 39 |
| Abstract: In the mouse and human, mRNA transcripts encoding the lymphocyte-specific protein tyrosine kinase p56lck are derived from two separate promoters resulting in heterogeneity in the 5' untranslated region sequence. The proximal promoter lies just 5' to the coding region for the gene and is active only in thymocytes. In contrast, the distal promoter lies 34 kilobases (kb) 5' in the human, and is active both in thymocytes and mature peripheral T cells. As previously reported, transgenic mice bearing functional proximal promoter sequence juxtaposed with the SV40 large T antigen gene invariably develop lymphoid tumors confined to the thymus. In the current work, transgenic mice bearing a 2.6-kb fragment of the human distal promoter fused to the SV40 large T antigen gene express large T antigen in thymocytes and in peripheral lymphoid cells, and develop tumors of both the thymus and the peripheral lymphoid organs. The ability of the human distal promoter to function appropriately in transgenic mice is consistent with the strong similarity observed between the mouse and human distal promoter sequences. With the exception of a single short interval that serves as a target for binding of nuclear factors, significant sequence similarity is not seen when the distal and proximal promoter sequences are compared. Hence, developmentally regulated, lineage-specific transcription of the lck gene is mediated by distinct promoter sequences that appear to be capable of functioning independently. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV WASHINGTON, DEPT BIOCHEM, SEATTLE, WA 98195 USA
2. UNIV WASHINGTON, DEPT IMMUNOL, SEATTLE, WA 98195 USA
3. HOWARD HUGHES MED INST, SEATTLE, WA 98195 USA
4. UNIV WASHINGTON, DEPT MED MED GENET, SEATTLE, WA 98195 USA
5. UNIV WASHINGTON, DEPT PEDIAT, SEATTLE, WA 98195 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: EV175 |
| ISSN: 0022-1007 |
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