Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages

Myungsoo Joo, Jeffrey G. Wright, Ning Hu Ning, Ruxana T. Sadikot, Young Park Gye, Timothy S. Blackwell, John W. Christman

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Expression of cyclooxygenase-2 (COX-2) is associated with the pathogenesis of inflammation and various cancers, including lung cancer. Yin Yang 1 (YY1) is a zinc-finger transcription factor that interacts with histone acetyltransferases and deacetylases for its transcriptional activity and also is involved in inflammation and tumorigenesis. We investigated whether YY1 regulates COX-2 expression. We located a possible YY1 binding site proximal to the transcription initiation site of the COX-2 promoter. Electrophoretic mobility shift assays show that YY1 bound to the putative YY1 site in vitro. To show biological relevance, we performed chromatin immunoprecipitation assays showing that lipopolysaccharide (LPS) treatment induced YY1 binding to the cognate site in the endogenous COX-2 promoter. Overexpression of YY1 in macrophages treated with either LPS or live Pseudomonas aeruginosa increased COX-2 transcriptional activity. Furthermore, YY1 enhanced COX-2 protein expression and prostaglandin D2 production elicited by LPS treatment. Mechanistically, we observed that LPS treatment resulted in disruption of an interaction between YY1 and p300, a histone acetyltransferase, but did not affect the interaction between YY1 and histone deacetylase 1/2. These data suggest that in response to LPS, YY1 dissociates from p300 and binds to the COX-2 promoter, contributing to COX-2 expression in an inflammatory milieu.

Original languageEnglish (US)
Pages (from-to)L1219-L1226
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume292
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

Keywords

  • Prostaglandin D
  • Protein modification

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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