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  • Describe factors that affect the affinity of general transcription factors for DNA and explain how this affects transcription rates.
    • transcriptional activators
      • promote regulators binding
      • also promotes RNA pol binding
      • recurit co activators
        • histone modifying enzymes
        • ATP-dependent chromatin remodelling complexes
        • histone chaperones
    • structure of Chromatin
      • can prevent access to promotors if wound tightly around Histones
        • neg charged Sug-pi backbone on DNA interacts with P+ DNA
        • Cis regulatory sequences = Face inwards
          • therefore Regulators bind with lower aff
            • Changes in shape of binding site due to associated protein binding
          • Changes in shape of binding site due to associated protein binding
      • How can the structure of chromatin change
        • Nucleosome slidding
          • needs : Histone chaperones, ATP-dep remodllers
            • NAP-1, SW12
        • Nucleosome eveiction
          • ATP dep, occurs alongside exchnage
        • Histone variant exchange
          • ATP dep remodllers and chaperones
        • histone tail mods
          • changes in A.A
            • (mainly lysine)
              • sumoylation and Ubq ( 0Q)
            • arginine- always maintains +, can be methylated
            • Serine- mainly Pi
          • histone tails help grip DNA
          • Effect = diff binding of mediator or GTFs
        • some mods compete as thier occur next to or at the smae A.A
    • Effects on multiple genes
      • 3D bending + binding to an insulator = prevent transcription initiation or progression
    • DNA methylation
      • Mainly T + C
      • mainly done by DNMTs
        • DNMT3a+b = de novo
        • DNMTs1 adds to daughter DNA during DNA synth
      • Occur a-lot in CpG islands
        • regulate tissue spef gene expression
        • Genomic imprinting
        • X-chromosome in activation
        • how do they effect expression
          • less nucleosomes
          • Close to TSS
          • inc TF binding sites
            • METH at exon 1 = recuirts TF
        • open up and recruit enzymes
      • recruits Inhibitory TF, disrupts TF binding, if at promotor = silencing
    • Epigenetic Cross talk
      • readers = mediator complex
      • Writers = enzymes that change mods
      • erasers= enzymes that remove mod eg de...
      • reg proteins bind to a CIS-REG seq
        • req writers
          • reader recognises mod
            • writer binds to reader= next mod on next chromosome
      • expression Histone tails meth= inhibit DNMT
      • inhibition - meth of DNA + tails = Mb Proteins= rec Tail modifers
      • break system
        • Barrier sequences= can stop the spread of changes
          • Tethering a chromatin domain to a large fixed site,   Strong binding barrier protein. c)  mediator complex containing chromatin modifying enzymes


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