ETS transcription factors regulate an enhancer activity in the third intron of TNF-alpha.

Published

Journal Article

We describe an enhancer site in the third intron of tumor necrosis factor alpha (TNF-alpha). A reporter construct containing the 5'-flanking region of the mouse TNF-alpha gene displayed weak activity when transfected into RAW264.7 macrophage-like cells. The addition of the third intron of TNF-alpha to this construct resulted in an enhancement of CAT protein. This enhancement was eliminated if a conserved 20-bp sequence was removed from the intron or if a dominant-negative ets-binding factor was co-transfected with the reporter gene. Mutations of this site that destroyed potential ets transcription factor binding sites had reduced transcriptional activity. The major transcription factor that bound to the oligonucleotide was confirmed to be GABP by supershift and competition analysis. In RAW264.7 cells, the binding was constitutive, however, in bone marrow-derived macrophages binding activity was shown to be interferon-gamma inducible. This may imply a role for ets transcription factors in the production of TNF-alpha.

Full Text

Duke Authors

Cited Authors

  • Tomaras, GD; Foster, DA; Burrer, CM; Taffet, SM

Published Date

  • July 1999

Published In

Volume / Issue

  • 66 / 1

Start / End Page

  • 183 - 193

PubMed ID

  • 10411007

Pubmed Central ID

  • 10411007

Electronic International Standard Serial Number (EISSN)

  • 1938-3673

International Standard Serial Number (ISSN)

  • 0741-5400

Digital Object Identifier (DOI)

  • 10.1002/jlb.66.1.183

Language

  • eng