ING4 mediates crosstalk between histone H3 K4 trimethylation and H3 acetylation to attenuate cellular transformation

Tiffany Hung1, Olivier Binda, Karen S Champagne

  • 1Department of Biology, Stanford University, Stanford, CA 94305, USA.

Molecular Cell
|February 4, 2009
PubMed

Insights

The Inhibitor of Growth 4 (ING4) protein links histone H3 lysine 4 trimethylation (H3K4me3) to gene expression and tumor suppression. This interaction enhances HBO1 histone acetyltransferase activity, promoting anti-cancer functions.

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • Chromatin dynamics are crucial in tumorigenesis, but the link between histone methylation and cancer is not fully understood.
  • ING4 (Inhibitor of Growth 4) is a tumor suppressor and a component of the HBO1 histone acetyltransferase (HAT) complex.

Purpose of the Study:

  • To investigate the role of ING4's interaction with histone H3 trimethylated at lysine 4 (H3K4me3) in gene expression and tumor suppression.
  • To elucidate the molecular mechanisms connecting H3K4 methylation, H3 acetylation, and tumor suppressor functions.

Main Methods:

  • Studied the interaction between the ING4 PHD finger and H3K4me3.
  • Assessed the impact of this interaction on HBO1 HAT activity and H3 acetylation at target promoters.
  • Evaluated ING4's role in apoptosis and anchorage-independent cell growth.

Main Results:

  • ING4 specifically recognizes H3K4me3 via its PHD finger, which is critical for ING4's gene expression and tumor suppressor functions.
  • ING4-H3K4me3 interaction enhances HBO1 HAT activity, leading to increased H3 acetylation at ING4 target promoters.
  • ING4 facilitates apoptosis and inhibits anchorage-independent growth, dependent on H3K4me3 interaction.

Conclusions:

  • Demonstrated a mechanism for crosstalk between H3K4 methylation and H3 acetylation.
  • Revealed a molecular link between chromatin modulation, specifically H3K4me3 recognition by ING4, and tumor suppressor activities.

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