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Related Experiment Video

Updated: Apr 17, 2026

Optimized Analysis of DNA Methylation and Gene Expression from Small, Anatomically-defined Areas of the Brain
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Methylomic trajectories across human fetal brain development.

Helen Spiers1, Eilis Hannon2, Leonard C Schalkwyk3

  • 1Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, United Kingdom;

Genome Research
|February 5, 2015
PubMed
Summary

The prenatal human brain undergoes significant DNA methylation changes, particularly in gene bodies and regions near CpG islands, highlighting epigenomic plasticity during fetal development. This study maps these dynamic epigenetic alterations across development.

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Area of Science:

  • Neuroscience
  • Epigenetics
  • Genomics

Background:

  • Epigenetic processes, including DNA methylation, are crucial for transcriptional regulation during development.
  • Dynamic DNA methylation patterns are essential for fetal brain development, as evidenced by methyltransferase expression and neurodevelopmental disorders linked to MECP2 mutations.
  • Limited understanding of temporal epigenome changes during human fetal brain development necessitates further investigation.

Purpose of the Study:

  • To comprehensively map genome-wide DNA methylation patterns throughout human fetal brain development.
  • To identify temporal changes in DNA methylation and their genomic locations.
  • To investigate sex-specific differences in DNA methylation trajectories during fetal brain development.

Main Methods:

  • Genome-wide DNA methylation quantification at approximately 400,000 sites.
  • Analysis of 179 human fetal brain samples spanning 23 to 184 days post-conception.
  • Weighted gene comethylation network analysis (WGCNA) to identify co-methylated gene modules.

Main Results:

  • Over 7% of DNA methylation sites exhibited significant changes during fetal brain development, with a trend towards hypomethylation with increasing fetal age.
  • Developmentally dynamic DNA methylation sites were enriched in gene bodies and CpG shores/shelves, but underrepresented in promoter regions.
  • Significant sex-based differences in DNA methylation were observed at autosomal sites, with some exhibiting distinct developmental trajectories.

Conclusions:

  • The prenatal period is characterized by substantial epigenomic plasticity in the human brain.
  • DNA methylation patterns undergo significant, spatially defined alterations during fetal brain development.
  • Sex-specific epigenetic programming contributes to neurodevelopmental trajectories.