Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Ets binding sites present in the promoter

D. Baillat, G. Leprivier, D. Régnier, N. Vintonenko, A. Bègue, D. Stéhelin, M. Aumercier

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Regulation of the gene expression of Stromelysin-1 (matrix metalloproteinase-3), a member of the matrix metalloproteinase family, is critical for tissue homeostasis. The Stromelysin-1 promoter is known to be transactivated by Ets proteins through palindromic head-to-head Ets binding sites (EBS), an unusual configuration among metalloproteinase promoters. Patterns of increased co-expression of Stromelysin-1 and Ets-1 genes have been observed in pathological processes such as rheumatoid arthritis, glomerulonephritis and tumor invasion. In this context, we show in a synovial fibroblastic model cell line (HIG-82), which is able to co-express Stromelysin-1 and Ets-1, that the EBS palindrome is essential for the expression of Stromelysin-1. More precisely, using electrophoretic mobility shift assays, DNA affinity purification and chromatin immunoprecipitation, we demonstrate that endogenous Ets-1, but not Ets-2, is present on this palindrome. The use of a dominant-negative form of Ets-1 and the decrease of Ets-1 amount either by fumagillin, an antiangiogenic compound, or by short interfering RNA show that the activation rate of the promoter and the expression of Stromelysin-1 correlate with the level of endogenous Ets-1. Thus, it is the first demonstration, using this cellular model, that endogenously expressed Ets-1 is actually a main activator of the Stromelysin-1 promoter through its effective binding to the EBS palindrome.

Original languageEnglish (US)
Pages (from-to)5764-5776
Number of pages13
JournalOncogene
Volume25
Issue number42
DOIs
StatePublished - Sep 21 2006

Keywords

  • Ets-1
  • Gene regulation
  • MMP-3
  • Synovial fibroblasts cell transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Baillat, D., Leprivier, G., Régnier, D., Vintonenko, N., Bègue, A., Stéhelin, D., & Aumercier, M. (2006). Stromelysin-1 expression is activated in vivo by Ets-1 through palindromic head-to-head Ets binding sites present in the promoter. Oncogene, 25(42), 5764-5776. https://doi.org/10.1038/sj.onc.1209583