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Regulation of p53 target gene expression by peptidylarginine deiminase 4

Pingxin Li1, Hongjie Yao, Zhiqiang Zhang

  • 1Center for Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802, USA.

Molecular and Cellular Biology
|May 29, 2008
PubMed

Insights

Peptidylarginine deiminase 4 (PAD4) represses p53 target genes, including p21. PAD4 depletion activates p21 expression, leading to cell cycle arrest and apoptosis, demonstrating its role in gene regulation.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Gene Regulation

Background:

  • Histone arginine methylation is linked to p53 target gene activation.
  • The reversal of this modification for gene repression remains unclear.

Purpose of the Study:

  • To investigate the role of peptidylarginine deiminase 4 (PAD4) in the repression of p53 target genes.
  • To elucidate the mechanism of PAD4 in regulating p53-mediated gene expression.

Main Methods:

  • Inhibition and depletion of PAD4.
  • Protein-protein interaction assays.
  • Chromatin immunoprecipitation (ChIP) assays.
  • RNA polymerase II activity assays.
  • Permanganate footprinting.

Main Results:

  • PAD4 inhibition/depletion elevated p53 target gene expression (e.g., p21), causing cell cycle arrest and apoptosis.
  • PAD4 interacts with p53 and is recruited to the p21 promoter in a p53-dependent manner.
  • PAD4 levels and histone modifications at the p21 promoter dynamically change following UV irradiation, impacting RNA polymerase II activity.

Conclusions:

  • PAD4 plays a significant role in repressing p53 target genes.
  • PAD4's recruitment and activity are crucial for regulating p53-dependent gene expression, particularly in response to DNA damage.
  • The findings reveal a novel mechanism for gene repression involving PAD4 in the p53 pathway.

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