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Related Experiment Videos

Epigenomics: mapping the methylome.

Ian M Wilson1, Jonathan J Davies, Michael Weber

  • 1British Columbia Cancer Research Centre, Vancouver, BC, Canada. wilson@bccrc.ca

Cell Cycle (Georgetown, Tex.)
|January 7, 2006
PubMed
Summary

This study introduces a new high-throughput method to map DNA methylation across the human genome. The technique reveals insights into X-chromosome methylation and epigenomic instability in cancer.

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Area of Science:

  • Genomics
  • Epigenetics
  • Molecular Biology

Background:

  • DNA methylation is crucial for development and disease, but its genomic distribution (the methylome) is not well understood.
  • Existing methods for assessing DNA methylation are often low-resolution or low-throughput.

Purpose of the Study:

  • To develop and validate a high-resolution, high-throughput platform for comprehensive human genome DNA methylation profiling.
  • To investigate genome-wide and locus-specific DNA methylation patterns in different biological contexts.

Main Methods:

  • Developed a platform combining methylated DNA immunoprecipitation (MeDIP) with array comparative genomic hybridization (array CGH).
  • Utilized whole genome tiling path BAC arrays and CpG island microarrays for simultaneous genome-wide and locus-specific analysis.

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  • Compared DNA methylation profiles between male and female DNA, and between cancer and non-cancer cell types.

    • Main Results:

    • Revealed unexpected hypomethylation of the inactive X-chromosome in gene-poor regions.
    • Identified differential methylation patterns between cancer and non-cancer cells, linking genetic and epigenetic instability.
    • Demonstrated epigenomic instability in lung cancer cells with concurrent genetic and epigenetic alterations near oncogenes.

    Conclusions:

    • The MeDIP-array CGH platform provides a powerful tool for high-resolution methylome analysis.
    • DNA methylation patterns differ significantly between sexes and are altered in cancer, highlighting epigenomic instability.
    • This approach offers new avenues for understanding gene misregulation in diseases like cancer.