Histone modification

HideShow resource information
View mindmap
  • Histone modification
    • Acetylation
      • Always positive regulation
      • N-terminal tails acetylated by co-activators:
        • CBP/p300
        • SAGA
          • VP16 recruits SAGA experiment
            • Viral protein 16 activator used alongside Gcn4 activator in studies - activation domain from VP16, DNA binding domain from Gcn4
            • On naked DNA templates in absence of SAGA there is SOME activation by VP16 as GTFs and TFIIB are recruited
            • When SAGA added it is recruied by VP16 + higher levels of transcription are observed
        • Gcn5
          • Recruited by Gcn4
        • PCAF
      • Acetylation of lysine residues (DNA acidic -ve , lysine basic +ve)
        • Acetylation reduces +ve charge so weakens attraction
          • Activators can then compete with histones
          • Chromatin remodellers can move nucleosomes
        • Transfer of acetyl groups from Acetyl Co-A
    • Ubiquitylation
      • Most commonly ubiquitinated:
        • H2A
          • Lys-119
            • Enriched in the satellite regions of genome
        • H2B
          • Lys-120
            • Binds to the gene body of transcriptionally active genes
            • By E2 - Rad6
            • By E3 - Bre1
        • Mainly mono
      • Ubiquitination enzymes
        • Addition
          • E1
          • E2
          • E3
            • Ubiquitin ligase - combines with ubiquitin-containing E2 ubiquitin-conjugating enzyme, reocgnises target protein and causes attachment of ubiquitin to a lysine on target via isopeptide bond
        • Removal
          • Isopeptidases
      • Regulates transcription via proteasome-dependent destruction of transcription factors
      • Activator or repressor?
        • REPRESSOR
          • Rad-6 mediated H2B ubiqu linked with silencing genes in budding yeast
          • Deletion of rad6 gene = defects in telomeric silencing
        • ACTIVATOR
          • Transcriptionally stalled hsp70 genes contain 50% ubiquitylated-H2A whereas regions of non-transcribed satellite DNA contian only 4% uH2A
          • In fission yeast the level of uH2B increases when gal1 gene is activated - but isopeptidases deubiquitylate H2B as gal1 mRNA product accumulates (drop in level of uH2B acts as a repressor)
      • How does it work?
        • May affect chromatin higher order structure, allowing machinery access
        • May act as signalling molecule to recruit other regulatory molecules
        • May impact other histone modifications which in turn regulate transcription
          • Evidence of ubiquitylation affection histone acetylation and methylation
    • The different histones
      • H1
        • Positioned between nucleosomes - bringing them closer together - even further condensation of chromatin
      • H2A
      • H2B
      • H3
      • H4
    • Phosphorylation
      • All 4 histone tails contain acceptor sites
        • Phosphorylated by kinases
        • Dephosphorylated by phosphatases
        • Can occur at:
          • Serine
          • Tyrosine
          • Threonine
          • H2B
            • Ser-32
          • H3
            • Ser-10
              • Promotes acetylation of H3K14 by Gcn5 + promotes Gcn5-mediated expression of genes in vivo
            • Ser-28
            • Thre-11
            • Phosphorylation of these residues associated with histone acetylation
            • Tyr-37
              • Phosphorylated by Wee1 enzyme - key component of cell cycle regulation
              • Mark important for suppression of replication-dependent core histone protein gene transcription
              • Phosphorylation directly blocks binding of transcriptional activator
          • H1
            • Can be phosphorylated at multiple residues
            • Involved in stabilisation of nucleosome and contributes to 30nm chromatin fibre
            • Role in chromatin relaxing --> gene transcription
            • Active rRNA promoters on H1 often phosphorylated
    • Methylation
      • Mainly at lysine residues
      • Can be mono/di/tri
      • Can alter affinity of histones for DNA
      • Can direct binding of additional TFs
        • H3k4me3
          • Associated with active genes and recognised by co-activators
          • Recruits TFIID by binding to TAF3 subunit where TAF1 binds acetylated histones
        • H3k79me3
          • Associated with repression and silencing genes
        • H3k27
          • Di
            • Activation
          • Tri
            • Repression
  • Untitled
    • Untitled

Comments

No comments have yet been made

Similar Biology resources:

See all Biology resources »See all Transcription resources »