New Insights into Protein Mutations Causing Rett Syndrome
Context:
Recent research from Rockefeller University has provided new insights into how MeCP2 (methyl-CpG-binding protein 2) interacts with DNA and chromatin.
More on News:
- MeCP2 is crucial for brain development, as it regulates thousands of genes. However, its exact functions and interactions with DNA have been elusive.
- Dysfunction of MeCP2 leads to Rett syndrome. Conversely, excess MeCP2 causes MeCP2 duplication syndrome, a similarly debilitating disorder.
Rett Syndrome
Key Findings:
- Researchers used a single-molecule technique to observe MeCP2’s behaviour on DNA.
- They tethered a single piece of DNA between plastic beads and incubated it with fluorescently labelled MeCP2 proteins. This setup allowed them to monitor the protein’s dynamic behaviour.
- The study revealed that MeCP2 binds to both methylated and unmethylated DNA but moves more slowly on methylated DNA.
- This slower movement helps MeCP2 recruit other regulatory proteins more efficiently to methylated DNA sites, directing its gene regulatory functions to specific genome locations.
- MeCP2 shows a strong preference for binding to nucleosomes (protein-DNA complexes) over bare DNA.
- This interaction stabilises nucleosomes and may suppress gene transcription, showing a new regulatory role for MeCP2.
- MeCP2’s preference for nucleosomes suggests it should be seen as a chromatin-binding protein, not just a methyl-DNA-binding one.
- The study indicates that nucleosomes play an active role in regulating genes, not just passively carrying DNA.
Implications:
- The findings offer potential new avenues for developing therapies for Rett syndrome.
- Understanding MeCP2’s functions better could lead to more effective treatments and deepen the knowledge of gene regulation mechanisms in neurological diseases.
Chromatin