Long Term Transcriptional Reactivation of Epigenetically Silenced Genes in Colorectal Cancer Cells Requires DNA Hypomethylation and Histone Acetylation
2011

Reactivating Silenced Genes in Colorectal Cancer Cells

publication Evidence: moderate

Author Information

Author(s): David Mossman, Rodney J. Scott, Michael Freitag

Primary Institution: University of Newcastle

Hypothesis

Can chromatin changes lead to long-term reactivation of epigenetically silenced genes in colorectal cancer cells after treatment with 5-aza-2′-deoxycytidine?

Conclusion

Hypomethylation alone is not enough to reactivate silenced genes; increased histone acetylation is also necessary for long-term gene reactivation.

Supporting Evidence

  • Increased H3 acetylation and H3K4 tri-methylation were associated with gene reactivation.
  • Three genes remained expressed 10 days post treatment, indicating long-term reactivation.
  • Hypomethylation at the transcriptional start site was crucial for sustained gene expression.

Takeaway

This study found that to wake up genes that were turned off in cancer cells, we need to change both the DNA and the proteins around it.

Methodology

Colorectal cancer cell lines were treated with 5-aza-2′-deoxycytidine, and changes in DNA methylation and histone modifications were assessed using bisulfite sequencing and Chromatin Immuno-Precipitation analysis.

Limitations

The study primarily focused on two colorectal cancer cell lines, which may limit the generalizability of the findings.

Participant Demographics

Colorectal cancer cell lines HCT116 and SW480 were used.

Statistical Information

P-Value

0.003, 0.017

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0023127

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