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Biophysical analysis and small-angle X-ray scattering-derived structures of MeCP2-nucleosome complexes
Chenghua Yang1, Mark J van der Woerd, Uma M Muthurajan
1Department of Biochemistry and Molecular Biology and Howard Hughes Medical Institute, Colorado State University, Fort Collins, CO 80523-1870, USA.
Nucleic Acids Research
|February 1, 2011
Summary
Methyl-CpG binding protein 2 (MeCP2) binds nucleosomes, forming distinct complexes. Its conformation changes based on DNA presence, impacting higher-order chromatin structure crucial for brain development.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Methyl-CpG binding protein 2 (MeCP2) is vital for post-natal brain development.
- Mutations in MeCP2 cause Rett syndrome, a leading cause of intellectual disability in girls.
- MeCP2 has multiple DNA and chromatin binding regions, but its structure is poorly understood.
Purpose of the Study:
- To investigate the interaction of MeCP2 with nucleosomes using solution-state methods.
- To determine the structural consequences of MeCP2 binding to nucleosomes with and without extra-nucleosomal DNA.
- To explore nucleosome conformational variability.
Main Methods:
- Small angle X-ray scattering (SAXS).
- Solution-state biophysical techniques.
- Ab initio envelope reconstructions from SAXS data.
Main Results:
- MeCP2 forms defined complexes with nucleosomes containing all four histones.
- MeCP2 adopts an extended conformation with nucleosomes lacking extra-nucleosomal DNA.
- Nucleosomes with extra-nucleosomal DNA lead to compact MeCP2-nucleosome complexes.
- SAXS revealed sequence-dependent nucleosome conformational variability.
Conclusions:
- MeCP2's interaction with nucleosomes is dynamic and context-dependent.
- The presence of extra-nucleosomal DNA significantly alters MeCP2-nucleosome complex structure.
- These findings provide insights into MeCP2's role in chromatin organization and its implications for Rett syndrome.
