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DNA methylation (promoter methylation)

Function: - DNA methylation is a ubiquitous biological process - it occurs in both prokaryotes & eukaryotes, including humans - in this process, DNA methyltransferases catalyze post-replicative addition of a methyl group to N6 of adenine or the C5 or N4 position of cytosine - S-adenosylmethionine (SAM) is the methyl donor - in higher eurkaryotes, DNA methylation occurs at the C5 position of cytosine to form 5'-methyl deoxycytosine in association with CpG islands - DNA methylation has a role in gene silencing - DNA methylation represses gene expression, through the action of either of 2 proteins that bind methylated CpG dinucleotides (MeCP1 & MeCP2) - MeCP1 requires methylation of several CpG dinucleotides for binding, whereas MeCP2 can bind a single methylated CpG dinucleotide - MeCP2 also complexes with the Sin3 repressor complex which that contains histone deacetylase activity. Physiology: - DNA methylation plays a role in genomic imprinting & embryonic development - DNA methylation serves, in part, to protect the genome against its own anti-restriction enzymes whose basic function is to hydrolyze naked sequences like those from viruses [4] Pathology: - aberrations in DNA methylation have been implicated in cancer & aging.

Specific

DNA hypermethylation GrimAge; DNAm GrimAge

General

methylation epigenetic clock

References

  1. Cancer, Principles and Practice of Oncology, 6th ed. DeVita et al (eds), Lippincot and Williams, Philadelphia, 2001, pg 492
  2. Fuks et al, Nature Genetics 24:88, 2000
  3. Kastan & Skapek, Molecular Biology of Cancer; the cell cycle, In: Cancer, Principles & Practice of Oncology, 6th edition, DeVita et al (eds), Lippincott & Williams, Philadelpha, 2001, pg 91
  4. Genes VII, Lewis B., Oxford University Press, NY, 2000
  5. L Stephen Coles, in GRG News Brief Feb 28, 2014 About J. Craig Venter's Lecture