15. Imprinting

• euchromatin has high histone acetylation, low dna methylation and H3K4 methylation
• heterochromatin has low histone acetylation, high dna methylation and H3K9 methylation

  • centromeres and telomeres are therefore permanently silenced
• DNMT1 is involved in maintenance methylation, replicates methylation from parental strand
• DNMT3a and 3b are involved in de novo methylation
• DNA acquires methylation from totipotent to unipotent stem cells
• embryonic methylation:

  • gametes are permanently silenced with high methylation
  • male immediately demethylates on fertilisation
  • female is much slower
  • morula is completely unmethylated
  • de novo methylation then occurs
• some genes are only expressed from either the maternal or paternal genome

  • affects expression but not transmission of alleles
  • two copies present but only one active - functional haploidy
• Igf2 = paternally expressed
• H19 = maternally expressed
• Igf2 expression

  • DMRs are methylated
  • DMR1 silencer is inactivated
  • DMR2 enhancer is activated
• H19 expression:

  • DMRs are hypomethylated
  • CTCF binds to DMR
  • H19 expression
• parent of origin gene expression imprints must be correctly set in gametes of every generation -> this is why gamete is fully demethylated and then de novo methylation occurs
• failure of genomic imprinting leads to developmental disorders like Prader-Willi and Angelman syndrome