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  <head>
    <title>091-03 Translation, protein targeting, chromatin, epigenetic memory, and regulated expression</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Translation, chromatin, and epigenetic control">
      <outline text="Genetic code and transfer RNA">
        <outline text="Nonoverlapping triplets: 61 sense, 3 stop"/>
        <outline text="Degenerate, but each codon one amino acid"/>
        <outline text="Reading frame set at initiation">
          <outline text="Non-triplet indels shift downstream codons"/>
        </outline>
        <outline text="Synthetases charge transfer RNAs using ATP">
          <outline text="Editing sites remove wrong amino acids"/>
          <outline text="Ribosome cannot check amino acid identity"/>
        </outline>
        <outline text="Wobble at the third codon position"/>
        <outline text="No simple universal codon speed code"/>
      </outline>
      <outline text="Ribosome and translation cycle">
        <outline text="Ribosomal RNA forms peptide bonds: a ribozyme"/>
        <outline text="Aminoacyl, peptidyl, and exit sites"/>
        <outline text="Cap-dependent scanning to a favourable AUG">
          <outline text="Upstream ORFs, structure, factor phosphorylation"/>
        </outline>
        <outline text="GTP factors deliver and translocate"/>
        <outline text="Polysomes, speed shapes folding"/>
        <outline text="Release factors at stop codons">
          <outline text="Premature stop: decay or truncation"/>
          <outline text="Readthrough is variable"/>
        </outline>
      </outline>
      <outline text="Energy and growth control">
        <outline text="ATP to AMP per activation, GTP in elongation"/>
        <outline text="Stress phosphorylates initiation factors">
          <outline text="Selected stress transcripts continue"/>
        </outline>
        <outline text="mTORC1 drives synthesis, suppresses autophagy"/>
        <outline text="AMP-activated kinase restrains at low energy"/>
        <outline text="Excess drives cancer, suppression causes wasting"/>
      </outline>
      <outline text="Protein targeting and maturation">
        <outline text="Signal peptide directs proteins to the ER">
          <outline text="Anchors and stop-transfer set topology"/>
          <outline text="Luminal domains become extracellular"/>
        </outline>
        <outline text="Nuclear signals, importins, Ran"/>
        <outline text="Mitochondria: amphipathic helix, translocases"/>
        <outline text="Peroxisomes can import folded proteins"/>
        <outline text="Mannose-6-phosphate tags lysosomal enzymes"/>
        <outline text="Folding, modification, assembly give function">
          <outline text="Mislocalisation causes disease despite activity"/>
        </outline>
      </outline>
      <outline text="Chromatin structure">
        <outline text="Octamer of H2A, H2B, H3, H4 pairs">
          <outline text="About 147 base pairs per nucleosome"/>
          <outline text="Linker DNA and H1 for higher order"/>
        </outline>
        <outline text="Nucleosome positions are dynamic"/>
        <outline text="Acetylation weakens charge, opens chromatin"/>
        <outline text="Methylation meaning depends on residue"/>
        <outline text="ATP remodellers slide, eject, replace"/>
        <outline text="Histone variants specialise regions"/>
        <outline text="Pioneer factors open closed chromatin"/>
      </outline>
      <outline text="DNA methylation and epigenetic memory">
        <outline text="Methylation mainly at CpG cytosines">
          <outline text="CpG-island methylation: stable repression"/>
        </outline>
        <outline text="Maintenance copies hemimethylated DNA"/>
        <outline text="De novo enzymes set new patterns"/>
        <outline text="TET enzymes support demethylation"/>
        <outline text="Heritable through mitosis, not immutable">
          <outline text="Germline and early embryo reprogramming"/>
          <outline text="Some imprints escape erasure"/>
        </outline>
      </outline>
      <outline text="Imprinting and X inactivation">
        <outline text="Expression by parent of origin">
          <outline text="Same region, different syndromes"/>
          <outline text="Gene specific, not genome-wide"/>
        </outline>
        <outline text="XIST coats the future inactive X">
          <outline text="Repressive chromatin forms Barr body"/>
        </outline>
        <outline text="Random inactivation gives mosaicism">
          <outline text="Escape genes and skewing modify disease"/>
        </outline>
      </outline>
      <outline text="Genome architecture and cell identity">
        <outline text="Cohesin extrudes loops"/>
        <outline text="Boundary proteins define TADs">
          <outline text="Lost boundary misactivates genes"/>
        </outline>
        <outline text="Lamina-associated regions repressed"/>
        <outline text="Factor networks: feedback, cross-repression"/>
        <outline text="Induced pluripotency resets somatic state">
          <outline text="Residual epigenetic memory may remain"/>
        </outline>
      </outline>
      <outline text="Interpreting regulated expression">
        <outline text="Blood methylation may reflect cell mix"/>
        <outline text="Human transgenerational inheritance hard to prove"/>
        <outline text="Expression measured at many layers">
          <outline text="Discordance between layers is common"/>
        </outline>
        <outline text="Chain of conditional permissions">
          <outline text="Function matters more than exon position"/>
        </outline>
      </outline>
    </outline>
  </body>
</opml>
