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dna_methylation.md

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DNA methylation basics

see Messerschmidt Review (2014)

  • undetectable in certain yeast, nematode, and fly species
  • in mamamals, DNA methylation is vital
    • mostly in symmetrical CpG context
    • single CpGs typically hypermethylated vs. unmethylated CpG islands --> low CpG density promoters are generally hypermethylated, yet active vs. high CpG density promoters that are inactive if methylated
    • transposons are repressed if methylated (esp. LINEs, LTRs), so are pericentromeric repeats
    • imprinted genes show parent-of-origin-specific DNA methylation (introduced during gamete differentiation) and subsequently allele-specific gene expression

DNA methylation machinery

de novo methylation

--> Dnmt3a, Dnmt3b

  • maternally provided (Dnmt3a)

methylation maintenance

--> Dnmt1

  • high affinity for hemimethylation
  • its deletion in mESCs causes hypotmethylation, but not a complete loss (lethal effect, though)

Dnmt2 is a misnomer: it methylates RNA, not DNA

Regions defined by DNA methylation

LMR UMR IMR PMD
me level 10-50% 0-10% mean: 57% 0-100%, seemingly disordered
size 271 bp 150 kb
abundance 20-40% of the genome
tissue-specific? yes yes, mostly yes (not present in ESC)
CpG content low high not defined variable
localization DHS overlap mostly promoters, CGIs mostly intragenic heterochromatin
reference Stadler (2011) Stadler (2011) Elliott (2015) Lister (2009), Gaidatzis (2014)