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Nucleosomes facilitate their own invasion.
1Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
Nature Structural & Molecular Biology
|July 20, 2004
Summary
Nucleosomes dynamically transition to expose DNA, enabling protein access. This conformational change facilitates protein binding to DNA, even when wrapped around histones.
Area of Science:
- Molecular Biology
- Epigenetics
- Chromatin Structure
Background:
- DNA within nucleosomes is sterically hindered, impeding access for essential cellular machinery.
- The mechanisms by which proteins recognize and access DNA target sites within nucleosomes remain largely unknown.
Purpose of the Study:
- To directly detect and characterize dynamic conformational transitions in nucleosomes.
- To quantify the equilibrium of nucleosome unwrapping under physiological conditions.
- To investigate how proteins interact with and access DNA within nucleosomes.
Main Methods:
- Direct detection of nucleosome conformational transitions.
- Quantification of equilibrium constants under physiological conditions.
- Assays to monitor protein binding to nucleosomal DNA.
Main Results:
- A dynamic equilibrium conformational transition in nucleosomes was directly detected.
- This transition significantly increases the distance between nucleosomal DNA ends and the histone core.
- The equilibrium constant for this transition was quantified under physiological conditions.
- LexA protein binding to its target site on nucleosomes shifts the equilibrium towards an unwrapped, accessible state, enabling stable binding.
Conclusions:
- Nucleosomes possess an inherent dynamic property that allows for DNA accessibility.
- This conformational flexibility enables proteins, regardless of their mechanism (energy-dependent or passive), to access buried DNA sequences.
- The findings provide a fundamental insight into how cellular processes involving DNA access within chromatin are regulated.