A Rahman Syndrome mutation in histone H1.4 disrupts chromatin compaction and phase separation - PubMed
3 hours ago
- #chromatin structure
- #Rahman syndrome
- #H1.4 mutation
- A mutation in histone H1.4 causes Rahman syndrome by altering the histone's carboxy-terminal domain, making it shorter and less positively charged.
- This mutation leads to more extended, flexible chromatin, with increased linker DNA accessibility and weakened nucleosome stacking.
- Mutated chromatin shows reduced ability to undergo phase separation (both liquid-liquid and liquid-solid), similar to histone-free chromatin.
- Simulations and FRET experiments confirm the mutated domain interacts less with linker DNA, causing a more open nucleosome structure.
- The mutation increases H1.4 mobility in cell nuclei, indicating weaker chromatin binding and suggesting a more relaxed chromatin state.
- These changes likely contribute to disease pathology by dysregulating gene expression, highlighting the role of the carboxy-terminal domain in chromatin compaction.