Journal
JOURNAL OF IMMUNOLOGY
Volume 171, Issue 7, Pages 3612-3619Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.7.3612
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Funding
- NHLBI NIH HHS [HL59838] Funding Source: Medline
- NIGMS NIH HHS [GM56492] Funding Source: Medline
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Using a phylogenetic approach, we identified highly conserved sequences within intron 3 of the human TNF-alpha gene. These sequences form cell type-specific DNase I hypersensitivity sites and display cell type-specific DNA-protein contacts in in vivo genomic footprints. Consistent with these results, intron 3 confers specific activity upon a TNF-alpha reporter gene in Jurkat T cells, but not THP-1 monocytic cells. Thus, using a combinatorial approach of phylogenetic analysis, DNase I hypersensitivity analysis, in vivo footprinting, and transfection analysis, we demonstrate that intronic regulatory elements are involved in the cell type-specific regulation of TNF-alpha gene expression.
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