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Regulatory factor for X-box family proteins differentially interact with histone deacetylases to repress collagen

Yong Xu1, Pritam K Sengupta, Edward Seto

  • 1Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.

The Journal of Biological Chemistry
|February 9, 2006
PubMed

Insights

Regulatory Factor for X-box (RFX) proteins repress collagen gene expression through two distinct pathways. RFX5/HDAC2 mediate interferon-gamma repression, while RFX1/HDAC1 handle methylation-mediated silencing.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Epigenetics

Background:

  • Regulatory Factor for X-box (RFX) proteins are known to repress collagen alpha2(I) gene (COL1A2) expression.
  • The precise mechanisms by which RFX proteins regulate collagen gene expression require further elucidation.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying RFX-mediated repression of collagen gene expression.
  • To identify distinct co-repressors and pathways involved in RFX1 and RFX5 function.

Main Methods:

  • In vitro association assays to identify co-repressor interactions.
  • Chromatin immunoprecipitation (ChIP) assays to assess in vivo protein recruitment.
  • Treatment with interferon-gamma, DNA methyltransferase inhibitor (5-aza-2'-deoxycytidine), and histone deacetylase inhibitor (Trichostatin A).

Main Results:

  • RFX5 interacts with HDAC2/mSin3B, and RFX1 interacts with HDAC1/mSin3A.
  • RFX5/HDAC2 mediate interferon-gamma-induced repression, while RFX1/HDAC1 are involved in methylation-dependent repression.
  • RFX protein acetylation by Trichostatin A activates collagen promoter activity.

Conclusions:

  • Two distinct pathways mediate RFX-driven collagen gene repression: RFX5/HDAC2 for interferon-gamma signaling and RFX1/HDAC1 for DNA methylation.
  • RFX protein acetylation influences collagen gene expression, suggesting a role for epigenetic modifications.

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