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An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
10:17

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Published on: November 3, 2010

Human DNA methylomes at base resolution show widespread epigenomic differences.

Ryan Lister1, Mattia Pelizzola, Robert H Dowen

  • 1Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Nature
|October 16, 2009
PubMed
Summary

This study maps DNA methylation genome-wide in human cells, revealing distinct patterns in embryonic stem cells versus fibroblasts. These findings offer new insights into epigenetic regulation during development and disease.

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Area of Science:

  • Epigenetics
  • Genomics
  • Developmental Biology

Background:

  • DNA cytosine methylation is a crucial epigenetic mark regulating gene expression, development, and disease.
  • Understanding methylation patterns is key to deciphering cellular processes.

Purpose of the Study:

  • To generate the first genome-wide, single-base-resolution maps of DNA methylation in human embryonic stem cells and fetal fibroblasts.
  • To compare these methylation maps with transcriptome and epigenomic data.
  • To investigate the role of non-CG methylation in embryonic stem cells.

Main Methods:

  • Genome-wide bisulfite sequencing for single-base resolution DNA methylation mapping.
  • Comparative analysis of DNA methylation, mRNA, small RNA, histone modifications, and DNA-protein interactions.
  • Analysis of methylation changes during induced differentiation and reprogramming.

Main Results:

  • Identified significant differences in DNA methylation composition and patterns between embryonic stem cells and fibroblasts.
  • Found that nearly 25% of methylation in embryonic stem cells was in a non-CG context, enriched in gene bodies.
  • Observed that non-CG methylation is dynamic, disappearing upon differentiation and restored in induced pluripotent stem cells.
  • Located hundreds of differentially methylated regions near pluripotency and differentiation genes.

Conclusions:

  • Human embryonic stem cells exhibit unique non-CG methylation patterns potentially involved in regulating pluripotency.
  • Fibroblasts show widespread hypomethylation linked to reduced transcriptional activity.
  • These reference epigenomes serve as a foundation for studying DNA methylation in human development and disease.