Histone demethylase KDM3B protects against ferroptosis by upregulating SLC7A11

FEBS Open Bio. 2020 Apr;10(4):637-643. doi: 10.1002/2211-5463.12823. Epub 2020 Mar 18.

Abstract

Ferroptosis is a type of adaptive cell death driven by cellular metabolism and iron-dependent lipid peroxidation. Though multiple genes (including SLC7A11 and GPX4) have been demonstrated to play key roles in ferroptosis, little is known about the epigenetic regulation of this process. Here, we report that KDM3B, a histone H3 lysine 9 demethylase, can protect against ferroptosis induced by Erastin, an inhibitor of SLC7A11. KDM3B overexpression in HT-1080 cells results in decreased histone H3 lysine 9 methylation. Furthermore, KDM3B upregulates the expression of SLC7A11 through cooperation with the transcription factor ATF4. In summary, we identify here KDM3B as a potential epigenetic regulator of ferroptosis.

Keywords: ATF4; KDM3B; SLC7A11; ferroptosis; histone; histone demethylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Amino Acid Transport System y+ / antagonists & inhibitors
  • Amino Acid Transport System y+ / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Epigenesis, Genetic
  • Ferroptosis / drug effects
  • Ferroptosis / genetics*
  • HEK293 Cells
  • Histones / metabolism
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / genetics
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Methylation
  • Piperazines / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • THP-1 Cells
  • Transfection
  • Up-Regulation / genetics*

Substances

  • ATF4 protein, human
  • Amino Acid Transport System y+
  • Histones
  • Piperazines
  • SLC7A11 protein, human
  • erastin
  • Activating Transcription Factor 4
  • Jumonji Domain-Containing Histone Demethylases
  • KDM3B protein, human