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Histones
🧬 About Histones
- 📦 DNA must be compacted to fit inside the nucleus - histones are the proteins that enable this packaging.
- 🧲 DNA is negatively charged (due to phosphate backbone), while histones are positively charged (rich in lysine & arginine) → strong ionic interaction.
- Drug-induced lupus erythematosus (SLE) is associated with autoantibodies against histone proteins.
- Histones are not only structural but also regulate gene expression by controlling access to DNA.
- DNA folding occurs at several levels, with histones playing key roles in the first stages.
🌀 DNA Folding Levels
- There are 3 major levels of folding (low → high order) to pack the 46 chromosomes into a tiny nucleus.
🔗 Nucleosomes
- DNA is wrapped around a histone octamer made of 2 × H2A, 2 × H2B, 2 × H3, and 2 × H4 → like “string wound around a reel”.
- One nucleosome core ≈ 147 base pairs of DNA wrapped around the histone core.
- Regulatory DNA sequences may be hidden by histones or revealed via histone modification (acetylation, methylation, phosphorylation).
📚 Chromatin
- Histone H1 binds outside the nucleosome cores and helps pack them into a higher-order structure.
- This forms the classic 30 nm fibre (solenoid).
- Chromatin exists in two forms:
- Euchromatin: loosely packed, transcriptionally active.
- Heterochromatin: tightly packed, transcriptionally silent.
🔧 Loop Formation
- Loops of chromatin are attached to a central scaffold made of non-histone proteins (e.g. topoisomerase II, scaffold proteins).
- This allows further compaction and organisation into metaphase chromosomes during cell division.
📌 Quick Summary
🧬 DNA wraps around histone octamers → nucleosomes. 📚 H1 condenses nucleosomes → 30 nm solenoid fibre. 🌀 Higher-order loops form on protein scaffolds → visible chromosomes. ⚠️ Clinical: Autoantibodies to histones → drug-induced lupus.
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