E2F1 K117 methylation by SETD6 disrupts BRD4-E2F1 binding and modulates E2F1 chromatin binding and gene regulation in

Gizem Tugce Ulu1, Margarita Kublanovsky2,3, Raz Shalev2,3

  • 1Institute of Biochemistry, University of Stuttgart, Allmandring 31, Stuttgart 70569, Germany.

Nucleic Acids Research
|January 16, 2026
PubMed

Insights

SETD6 protein lysine methyltransferase monomethylates transcription factor E2F1, impacting gene regulation and oncogenic phenotypes in prostate cancer. This methylation switch controls E2F1

Area of Science:

  • Molecular Biology
  • Epigenetics
  • Cancer Research

Background:

  • SETD6 (SET domain-containing protein 6) is a lysine methyltransferase involved in cellular processes, including cancer.
  • SETD6 monomethylates the transcription factor E2F1, but the functional outcomes remain largely unknown.
  • E2F1 plays a critical role in cell cycle regulation and cancer development.

Purpose of the Study:

  • To investigate the role of SETD6-mediated E2F1 K117 monomethylation in prostate cancer.
  • To elucidate the mechanism by which SETD6 methylation affects E2F1 function and chromatin interaction.
  • To determine the impact of E2F1 methylation on oncogenic phenotypes.

Main Methods:

  • Chromatin binding assays
  • Gene expression analysis
  • Biochemical and cellular assays
  • Genomic assays

Main Results:

  • SETD6-mediated E2F1 methylation alters E2F1's chromatin binding and gene upregulation profiles.
  • E2F1 methylation by SETD6 influences oncogenic phenotypes in prostate cancer cells.
  • SETD6-mediated K117 methylation prevents E2F1 K117 acetylation, regulating E2F1-BRD4 interaction.

Conclusions:

  • SETD6-mediated K117 methylation acts as a molecular switch, controlling E2F1's interaction with BRD4 via a methylation/acetylation mechanism.
  • This regulatory switch modulates E2F1's chromatin binding and downstream gene expression, affecting cellular phenotypes.
  • The findings suggest a broader role for SETD6 in regulating transcription factor activity through similar methylation/acetylation mechanisms.

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