Tissue-specific Activity of the γc Chain Gene Promoter Depends upon an Ets Binding Site and Is Regulated by GA-binding Protein
The γc chain is a subunit of multiple cytokine receptors (interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15), the expression of which is restricted to hematopoietic lineages. A defect in γc leads to the X-linked severe combined immunodeficiency characterized by a block in T cell differentiation. In...
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Published in | The Journal of biological chemistry Vol. 271; no. 25; p. 14849 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
21.06.1996
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Online Access | Get full text |
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Summary: | The γc chain is a subunit of multiple cytokine receptors (interleukin (IL)-2, IL-4, IL-7, IL-9, and IL-15), the expression
of which is restricted to hematopoietic lineages. A defect in γc leads to the X-linked severe combined immunodeficiency characterized
by a block in T cell differentiation. In order to better characterize the human γc promoter and define the minimal tissue-specific
promoter region, progressive 5â²-deletion constructs of a segment extending 1053 base pairs upstream of the major transcription
start site were generated and tested for promoter activity in various hematopoietic and nonhematopoietic cell types. The â1053/+34
construct allowed promoter activity only in cells of hematopoietic origin, and tissue specificity was conserved in all other
constructs tested. The region downstream of â90 appeared critical for basal promoter activity. It contains two potential Ets
binding sites conserved in the murine γc promoter gene, one of which was found essential for functional promoter activity
as determined by mutational analysis. The functional Ets binding site was found to bind Ets family proteins, principally GA-binding
protein and Elf-1 and could be transactivated by GABPα and -β synergistically. These results indicate that, as already reported
for the IL2Rβ promoter, GA-binding protein is an essential component of γc basal promoter activity. Although GABP expression
is not restricted to the hematopoietic lineage, its interaction with other specific factors may contribute to the tissue-specific
expression of the γc gene. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.271.25.14849 |