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LSM2232 - Epigenetics (Nucleotide level (Nucleotide methylation (CpG…

- - - - Upstream of coding genes --> Signal a gene is near
      - Methylation = deactivate genes (C methylation)
      - Replication would turn a fully methylated CpG island into hemimethylated
      - Facilitating enzymes
        
        de novo methyltransferase - methylate unmethylated sequence
        
        Maintenance methyltransferase = switch hemimethylated sites to fully methylated sites
        
        Demethylase = remove methyl groups
        
        TET - convert 5-methylcytosine (methylated sequence) to 5-hydroxymethylcytosine for DNA methylation :pen:
    - - Heritable methylation pattern
      - Different in paternal and maternal alleles' methylation pattern
      - eg. Igf2 & H19 genes
        
        Paternal gene
        
        No CTCF binds to ICR
        
        Enhancer binds to Igf2 --> Igf2 active, H19 inactive
        
        Methylated ICR (imprinting control region)
        
        Maternal gene
        
        CTCF binds to ICR, blocking enhancer binding to Igf2
        
        H19 active, Igf2 inactive
        
        Unmethylated ICR (imprinting control region)
  - - - Rerpressor
        
        Polycomb group proteins (PcG)
        
        Binds to nucleosomes
        
        Perpetuates :!: repression even when repressors is lost, not initiate repression
        
        Binding site=PRE (polycomb response element) nucleotide sequence
      - Activator
        
        Trithorax group protein (trxG)
        
        Antagonize PcG activities
        
        Also bind to PRE, opposing effect from Pc-G
- - - - Acetylation=> Gene activation
        
        All newly synthesised histones , :!: at specific site
        
        HAT (histone acetyltransferase)
        
        Acetylate Lysine
        
        Usually associated with transcription activators :star:
        
        eg. PCAF (co-activator)
        
        Activate transcription
      - Deacetylation
        
        Stabilise nucleosome structure/Deactivate transcription
        
        HDAC (histone deacetylase)
        
        Usually associated with transcription repressors :star:
        
        RPD3 (Reduced Potassium Dependency) - co-repressor
        
        Target different type of histone, commonly H3 & H4 :!:
        
        Histones deacetylated after binding to DNA (nucleosome forming)
        
        Act on histone tail - N-terminal :!:
    - - Connected to nucleotide methylation :!:
      - Deactivate genes :star:
      - Recruit chromatin-modifying complexes :!: :!!:
  - - - Insulator
    - - PEV (Posiion Effect Variegation)
        
        Deacivate genes
        
        Regulators
        
        Suppress PEV mutations (activate geneS)
        
        HMT :star:
        
        HDAC :star:
        
        HP1 :star:
        
        Enhance PEV mutations (deactivate genes)
        
        Swi/Snf :star:
        
        Zeste :star:
        
        Brahma :star:
- - - - Halve expression of 2 female X
    - - Inactivate one female X
        
        Condensation into constitutive heterochromatin by condensins
        
        Occurs during 32-cell embryonic stage
        
        Random --> 16 X1 inactive, 16 X2 inactive cells :!:
        
        X inactivation center (Xic) - DNA sequence :star:
        
        Xist RNA (only on inactive X)
        
        Xist recruits polycomb
        
        Inactive X
      - Inactivate n-1 X if >2X present
        
        Only 1 X active
    - - Double expression of X in male