Capturing Structural Heterogeneity in Chromatin Fibers

Chromatin fiber organization is implicated in processes such as transcription, DNA repair and chromosome segregation, but how nucleosomes interact to form higher-order structure remains poorly understood. We solved two crystal structures of tetranucleosomes with approximately 11-bp DNA linker length...

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Bibliographic Details
Published in:Journal of molecular biology 2017-10, Vol.429 (20), p.3031-3042
Main Authors: Ekundayo, Babatunde, Richmond, Timothy J., Schalch, Thomas
Format: Article
Language:English
Subjects:
Chromatin - chemistry
Chromatin - metabolism
chromatin structure
Crystallography, X-Ray
Microscopy, Electron
Nucleic Acid Conformation
nucleosomes
Nucleosomes - chemistry
Nucleosomes - metabolism
Protein Conformation
tetranucleosomes
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Summary:Chromatin fiber organization is implicated in processes such as transcription, DNA repair and chromosome segregation, but how nucleosomes interact to form higher-order structure remains poorly understood. We solved two crystal structures of tetranucleosomes with approximately 11-bp DNA linker length at 5.8 and 6.7 Å resolution. Minimal intramolecular nucleosome–nucleosome interactions result in a fiber model resembling a flat ribbon that is compatible with a two-start helical architecture, and that exposes histone and DNA surfaces to the environment. The differences in the two structures combined with electron microscopy reveal heterogeneous structural states, and we used site-specific chemical crosslinking to assess the diversity of nucleosome–nucleosome interactions through identification of structure-sensitive crosslink sites that provide a means to characterize fibers in solution. The chromatin fiber architectures observed here provide a basis for understanding heterogeneous chromatin higher-order structures as they occur in a genomic context. [Display omitted] •How do nucleosomes pack in chromatin fibers?•We crystallized a range of tetranucleosomes and determined two crystal structures.•Tetranucleosome structures reveal highly accessible nucleosome surfaces.•Site-specific crosslinking monitors chromatin fiber architecture.•Structures and crosslinking reveal chromatin fiber heterogeneity at high resolution.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2017.09.002