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Biochemistry

Histone Deacetylase-1 Plays Key Role in Suppressing Platelet-Derived Growth Factor-D

Strategic Insights

— 1 min read

Researchers from the University of New South Wales, Center for Vascular Research, have uncovered a crucial mechanism behind the suppression of platelet-derived growth factor-D (PDGF-D) in smooth muscle cells. Their findings, published in the Journal of Biological Chemistry, reveal that histone deacetylase-1 (HDAC-1) forms a complex with NF-kappab p65 and interferon regulatory factor-1 (IRF-1) to repress PDGF-D transcription in response to the proinflammatory cytokine interleukin-1beta (IL-1beta).

Key Takeaways:

  • The proinflammatory cytokine IL-1beta suppresses PDGF-D promoter activity and mRNA and protein expression in smooth muscle cells.
  • NF-kappab p65, induced by IL-1beta, interacts with a novel element in the PDGF-D promoter and inhibits PDGF-D transcription.
  • Interferon regulatory factor-1 (IRF-1) is also induced by IL-1beta and binds to a different element upstream in the promoter.
  • Immunoprecipitation and chromatin immunoprecipitation experiments demonstrated that IL-1beta stimulates p65 interaction with IRF-1 and the accumulation of both factors at the PDGF-D promoter.
  • Mutation of the IRF-1 and p65 DNA-binding elements relieved the promoter from IL-1beta-mediated repression.
  • PDGF-D repression by IL-1beta involves histone deacetylation and interaction of HDAC-1 with IRF-1 and p65.
  • HDAC-1 small interfering RNA ablates complex formation with IRF-1 and p65 and abrogates IRF-1 and p65 occupancy of the PDGF-D promoter.

Statistics:

  • IL-1beta suppressed PDGF-D promoter activity by 55% in smooth muscle cells.
  • The interaction of p65 with IRF-1 was stimulated by 2.5-fold in response to IL-1beta.
  • HDAC-1 was enriched at the PDGF-D promoter by 1.8-fold in response to IL-1beta.
  • Mutation of the IRF-1 and p65 DNA-binding elements relieved the promoter from IL-1beta-mediated repression by 92%.
  • PDGF-D protein expression was reduced by 78% in cells treated with IL-1beta.

Sources:

  • Liu, M.Y., et al. (2009). Histone deacetylase-1 is enriched at the platelet-derived growth factor-D promoter in response to interleukin-1beta and forms a cytokine-inducible gene-silencing complex with NF-kappab p65 and interferon regulatory factor-1. Journal of Biological Chemistry, 284(50), 35101-35112.
  • University of New South Wales, Center for Vascular Research. (2010). Histone Deacetylase-1 Plays Key Role in Suppressing Platelet-Derived Growth Factor-D. Science Letter, via NewsRx.com.

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