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Gene Involves a Functional and Highly Conserved Chromatin Signature in Intron 3 1
Center for Blood Research and Department of Medicine, Harvard Medical School, Boston, MA 02115
Using a phylogenetic approach, we identified highly conserved sequences within intron 3 of the human TNF-
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- 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- gene expression.
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