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Local DNA Sequence Controls Asymmetry of DNA Unwrapping from Nucleosome Core Particles

Alexander W Mauney¹, Joshua M Tokuda¹, Lisa M Gloss²

¹School of Applied and Engineering Physics, Cornell University, Ithaca, New York.

Biophysical Journal

|August 4, 2018

Summary

DNA accessibility in nucleosome core particles (NCPs) is crucial for gene regulation. DNA sequence variations significantly impact how DNA unwraps from histones, affecting cellular processes.

Area of Science:

Structural biology
Molecular genetics
Biophysics

Background:

DNA is packaged into nucleosome core particles (NCPs) around histone proteins.
DNA accessibility within NCPs is vital for gene transcription and regulation.
Histone and DNA properties influence NCP accessibility.

Purpose of the Study:

To investigate how DNA sequence variations affect DNA unwrapping from NCPs.
To understand the role of salt concentration in NCP destabilization and DNA unwrapping pathways.
To explore sequence-dependent differences in DNA unwrapping dynamics.

Main Methods:

Small angle X-ray scattering with contrast variation to study DNA unwrapping.
Coarse-grained Monte Carlo simulations for sequence-dependent structural modeling.
Ensemble optimization methods to analyze structural ensembles and electrostatic interactions.

Main Results:

Salt concentration induces destabilization of NCPs, leading to multiple unwrapped DNA states.
DNA sequence variations exhibit distinct unwrapping pathways and equilibrium constants.
Identified correlations between specific DNA sequence features and unwrapping behaviors.

Conclusions:

DNA sequence is a critical determinant of nucleosome core particle stability and DNA accessibility.
Understanding sequence-dependent unwrapping provides insights into transcription regulation mechanisms.
The study reveals sequence-specific modulation of DNA-histone interactions.

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