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N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation

Chengchuan Ma1,2, Rong Niu1, Tianxiao Huang1

  • 1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.

Nature Cell Biology
|December 5, 2018
PubMed

Insights

N6-methyldeoxyadenine (6mA) epigenetic marks in C. elegans transmit mitochondrial stress adaptations to progeny. This DNA modification regulates stress response genes, ensuring inherited resilience.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Genetics

Background:

  • N6-methyldeoxyadenine (6mA) is a bacterial DNA methylation mark involved in restriction-modification systems.
  • While detected in eukaryotes, the physiological role of 6mA in these organisms remains largely unknown.
  • DNA 5mC methylation changes are linked to transgenerational inheritance, suggesting 6mA might also carry inheritable information.

Purpose of the Study:

  • To investigate the physiological function of 6mA in eukaryotes.
  • To explore the potential role of 6mA in transgenerational inheritance of stress responses.
  • To determine if 6mA is involved in transmitting mitochondrial stress adaptations in C. elegans.

Main Methods:

  • Utilized Caenorhabditis elegans as a model organism.
  • Investigated the roles of histone H3K4me3 and DNA 6mA modifications.
  • Analyzed global DNA 6mA levels following mitochondrial perturbation.
  • Examined the impact of 6mA on mitochondrial stress response gene transcription.

Main Results:

  • Histone H3K4me3 and DNA 6mA are essential for transmitting mitochondrial stress adaptations to offspring.
  • Global DNA 6mA levels significantly increase after mitochondrial stress.
  • 6mA modification targets mitochondrial stress response genes, enhancing their transcription.
  • This process alleviates mitochondrial stress in progeny.

Conclusions:

  • 6mA functions as a regulated epigenetic mark in C. elegans.
  • 6mA plays a crucial role in modulating stress response and signaling transgenerational inheritance.
  • These findings highlight 6mA's importance in inherited stress resilience.

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