Aging, Environment, & DiseaseDNA Methylation and Hydroxymethylation

Different DNA Hypomethylation Patterns in Cancer and Aging

Hypomethylation in cancer and agingThe risk of developing cancer increases with age [1]. The mechanisms that increase the prevalence of cancer with age are not fully understood. Several studies have found the presence of polycomb-target gene promoter hypermethylation in aging and cancer [2], [3]. Perez et al researched whether aging and cancer share changes in DNA hypomethylation, in addition to hypermethylation.

DNA CpG methylation was analyzed in healthy and tumoral tissue from patients of varying ages that have breast, kidney, thyroid, skin and brain cancers. In both aging and cancer, hypomethylated CpG sites were enriched in introns and open sea locations, areas greater than 4 kb from a CpG island, while depleted in CpG islands and gene promoters. In contrast, density of hypermethylated CpG sites was varied in cancer, while in aging these sites were concentrated in CpG islands and gene promoters.

Changes in CpG methylation were more similar between tissues in regard to cancer, when compared to aging. In aging and cancer, CpG hypermethylation clustered in regions with H3K27me3 and H3K9me3 repressive histone modifications, H3K4me1 and H3K4me3 active histone modifications, polycomb repressive domains and repeat/ZNF domains. There was much more variability in hypomethylated CpG sites between aging and cancer. For example, in cancer hypomethylation was often observed at heterochromatic regions but in aging, these sites were more likely to be found at DNA enhancers.

The above paper found that cancer and aging have similar DNA hypermethylated regions but vary greatly on DNA hypomethylated regions. This could mean that hypomethylation in cancer may have a different effect on cell function than in aging. Perez et al found a complex relationship between methylation changes in aging and cancer that needs to be researched further to determine its complete function in the progression of cancer.

Original Article

  1. R. F. Pérez, J. R. Tejedor, G. F. Bayón, A. F. Fernández, and M. F. Fraga, “Distinct chromatin signatures of DNA hypomethylation in aging and cancer.,” Aging cell, Mar. 2018.

References

  1. J. P. de Magalhães, “How ageing processes influence cancer.,” Nature reviews. Cancer, vol. 13, no. 5, pp. 357–365, May 2013.
  2. Y. Schlesinger et al., “Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.,” Nature genetics, vol. 39, no. 2, pp. 232–236, Mar. 2007.
  3. V. K. Rakyan et al., “Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains.,” Genome research, vol. 20, no. 4, pp. 434–439, Apr. 2010.
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Aaron Barnett

Aaron Barnett