The first intron of the human α2(I) collagen gene (COL1A2) contains a novel interferon-γ responsive element

Shizuko Tanaka, Francesco Ramirez

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Cell transfection assays have shown that several transcription factors can mediate interferon-γ (INF-γ) inhibition of the human α2(I) collagen gene (COL1A2) by binding distinct cis-acting elements in the proximal promoter. Recent transgenic work, on the other hand, has identified a strong repressor in the first intron of COL1A2 that includes a binding site for interferon regulatory factors (IRFs). Here we present evidence from cell transfection experiments indicating that this IRF-binding site (IF3) is a novel target of the pathways elicited by INF-γ to blunt transcription from the COL1A2 promoter. First, we showed that INF-γ stimulates the production of IRF-1 transcripts, as well as the formation of an IRF-1 containing complex at the FI3 element. Second, we demonstrated that IRF-1 over-expression inhibits COL1A2 promoter activity specifically through the action of FI3, in addition to decreasing the steady-state levels of the endogenous COL1A2 mRNA. Third, we documented that INF-γ treatment of cultured fibroblasts increases binding of IRF-1 to FI3 in the endogenous COL1A2 gene. Together our findings further extend the list of transcription factors involved in INF-γ inhibition of COL1A2 gene expression.

Original languageEnglish
Pages (from-to)185-189
Number of pages5
JournalMatrix Biology
Volume26
Issue number3
DOIs
StatePublished - Apr 2007
Externally publishedYes

Keywords

  • COL1A2 regulation
  • Fibrosis
  • INF-γ
  • IRF-1
  • Transcriptional repression

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