Histones

• Structure & Composition
  • Small, basic proteins rich in Lysine and Arginine (positively charged).
  • Bind to the negatively charged phosphate backbone of DNA.
  • Nucleosome Core: Octamer consisting of (H2A, H2B, H3, H4) x 2. DNA wraps around this core ~1.75 times.
  • Histone H1 (Linker): Binds to the nucleosome and “linker DNA” to stabilize the chromatin fiber. It is outside the core octamer. t
• Epigenetic Regulation
  • Acetylation
    • Performed by Histone Acetyltransferases (HATs).
    • Removes (+) charge from lysine $\to$ relaxes DNA coiling $\to$ Euchromatin.
    • Result: ↑ Transcription (“Histone Acetylation makes DNA Active”).
  • Deacetylation
    • Performed by Histone Deacetylases (HDACs).
    • Restores (+) charge $\to$ tightens DNA coiling $\to$ Heterochromatin.
    • Result: ↓ Transcription (Gene silencing).
  • Methylation
    • Histone methylation can repress or activate transcription depending on the specific location.
    • Contrast with DNA Methylation (CpG islands): “Methylation makes DNA Mute” (silencing/imprinting).
• Clinical Relevance
  • Drug-Induced Lupus Erythematosus (DILE)
    • Classic triggers: Hydralazine, Procainamide, Isoniazid.
    • Often seen in Slow Acetylators.
    • Serology: Anti-histone antibodies are characteristic (>95% sensitive).
  • Huntington Disease
    • Mechanism involves Histone Deacetylation $\to$ silencing of genes necessary for neuronal survival $\to$ neuronal cell death.
  • Mitochondrial DNA
    • Unlike nuclear DNA, mitochondrial DNA is circular and does not utilize histones.