DNA methylation

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  • DNA methylation
    • The 5' position of cytosines in CpG dinucleotides can be methylated to methylcytosine
      • Genes with the POTENTIAL to be transcribed are NOT methylated
      • During differentiation genes are marked as being "inactive" by methylation + kept like this for life
    • Requires 2 enzymes:
      • Maintenance Methylase (Hemi-methylases)
        • Pass methylation patterns on after DNA replication
        • Methylating cytosine residues on 1 strand when other is methylated
        • Continues through life-time to maintain pattern of methylation
        • A mutation in this gene will activate gene expression
          • Ectopic expression of genes
            • Can lead to cancer - demethylated oncogenes switched ON
      • De novo methylases
        • First methylate DNA. Mechanisms unknown
    • Methyl-CpG
      • HDACs recruited
        • Methylating, repressive marks promoted on histones
          • Silencing by heterochromatin protein 1 (HP1)
    • Abberant DNA methylation
      • Contributes to disease - E.g. the leukemia myelodysplastic syndromes (MDS)
      • 5-azacytidine + 5-aza-2'deoxycytidine can be incorporated into DNA artificially and cannot be methylated
        • Leads to activation of gene expression
          • Therefore can be used as a drug to reverse effects of abberant DNA methylation
            • Contributes to disease - E.g. the leukemia myelodysplastic syndromes (MDS)

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