Cytokine-induced changes in chromatin structure and in vivo footprints in the inducible NOS promoter

Jane K. Mellott, Harry S. Nick, Michael F. Waters, Timothy R. Billiar, David A. Geller, Sarah E. Chesrown*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Transcription of the human inducible nitric oxide synthase (iNOS) gene is regulated by inflammatory cytokines in a tissue-specific manner. To determine whether differences in cytokine-induced mRNA levels between pulmonary epithelial cells (A549) and hepatic biliary epithelial cells (AKN-1) result from different protein or DNA regulatory mechanisms, we identified cytokine-induced changes in DNase I-hypersensitive (HS) sites in 13 kb of the iNOS 5′-flanking region. Data showed both constitutive and inducible HS sites in an overlapping yet cell type-specific pattern. Using in vivo footprinting and ligation-mediated PCR to detect potential DNA or protein interactions, we examined one promoter region near -5 kb containing both constitutive and cytokine-induced HS sites. In both cell types, three in vivo footprints were present in both control and cytokine-treated cells, and each mapped within a constitutive HS site. The remaining footprint appeared only in response to cytokine treatment and mapped to an inducible HS site. These studies, performed on chromatin in situ, identify a portion of the molecular mechanisms regulating transcription of the human iNOS gene in both lung- and liver-derived epithelial cells.

Original languageEnglish
Pages (from-to)L390-L399
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 24-3
StatePublished - Mar 2001
Externally publishedYes


  • Deoxyribonuclease I-hypersensitive sites
  • Inflammatory cytokines
  • Liver epithelial cells
  • Lung epithelial cells
  • Nitric oxide synthase


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