DNA methylation and hydroxymethylation have distinct genome-wide profiles related to axonal regeneration

EPIGENETICS, 2021 · DOI: https://doi.org/10.1080/15592294.2020.1786320 · Published: January 2, 2021

Simple Explanation

This study investigates the roles of DNA methylation (5mC) and hydroxymethylation (5hmC) in axonal regeneration following spinal cord injury. These epigenetic marks are sensitive to environmental factors like folate. The researchers found that 5mC and 5hmC have distinct locations and functions in the genome related to axonal regeneration. This suggests they play different roles in the healing process. The research also found that ancestral folate supplementation affects both 5mC and 5hmC levels, influencing the transgenerational inheritance of enhanced axonal regeneration.

Study Duration

Not specified

Participants

Adult F3 male rats with enhanced regeneration of injured spinal axons or controls

Evidence Level

Not specified

Key Findings

1
Differentially hydroxymethylated regions (DhMRs) and differentially methylated regions (DMRs) are largely unique, with distinct functions in axonal regeneration.
2
Changes in 5hmC and 5mC levels correlate with altered transcript levels and are linked to genes involved in axon growth and development.
3
A significant enrichment of transcription factor binding sites is observed among the differentially hydroxymethylated and methylated sites, potentially explaining disruptions in gene expression.

Research Summary

The study examines the distinct roles of 5hmC and 5mC in spinal cord injury and regeneration, specifically in the context of a folate-induced transgenerational phenotype. It identifies more than 2,800 sites throughout the genome with regeneration-related 5hmC and 5mC levels, many of which appear to be functional by altering gene expression. The findings suggest that these DNA methylation modifications could be potential therapeutic targets for spinal cord and CNS injuries.

Practical Implications

Therapeutic Targets

The findings support novel investigations into CNS injury mechanisms and may provide candidate therapeutic substrates for individuals suffering from spinal cord and CNS injury and disease.

Transgenerational Epigenetics

The study highlights the importance of considering transgenerational epigenetic effects in the context of spinal cord injury and regeneration.

Folate Supplementation

The research suggests that ancestral folate supplementation can have long-lasting effects on DNA methylation and axonal regeneration.

Study Limitations

1
The annotated neuronal enhancers were taken from the mouse genome, with limited relevant annotation of the rat genome.
2
Conversion of the DhMR and DMR genomic coordinates to the mouse genome (mm9) is imperfect.
3
The molecular mechanism of mCH methylation in axonal regeneration remains to be clarified.

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