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Understanding nucleosome dynamics and their links to gene expression and DNA replication

Nature Reviews Molecular Cell Biology volume 18, pages 548–562 (2017)Cite this article

Subjects

Key Points

  • Nucleosomes are highly dynamic nucleoprotein complexes involved in almost every genomic process across all eukaryotic organisms.

  • Both individual histone and full nucleosome turnover is under tight regulation that is mediated by a diverse set of chaperones and remodellers.

  • Subnucleosomal structures are dynamically generated as intermediaries during transcription and replication and are predicted to exist throughout the genome at specific loci.

  • The precise positioning of a nucleosome is a highly regulated process owing to numerous chaperones and remodeller complexes. Perturbations of nucleosome positioning have been linked to changes in gene expression levels.

  • Nucleosome disassembly and inheritance is carefully regulated during DNA replication with the restoration of the pre-replication positioning linked to transcription.

Abstract

Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases. It is now known that these dynamics regulate diverse cellular processes ranging from gene transcription to DNA replication and repair.

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Figure 1: Nucleosome organization as a combination of nucleosome occupancy and positioning.
Figure 2: Nucleosome occupancy as a function of histone turnover.
Figure 3: Determinants of nucleosome positioning.
Figure 4: Examination of nucleosome substructures and methods to detect them.
Figure 5: Nucleosome dynamics of transcription at ribosomal protein genes.
Figure 6: Nucleosome dynamics of DNA replication.

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Acknowledgements

The authors thank the members of B. F. Pugh's laboratory and the Center for Eukaryotic Gene Regulation for their helpful comments and feedback. This work was supported by the US National Institutes of Health (NIH) grant GM059055.

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  1. Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, 16802, Pennsylvania, USA

    William K. M. Lai & B. Franklin Pugh

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Correspondence to B. Franklin Pugh.

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Competing interests

B.F.P. has a financial interest in Peconic, LLC, which utilizes the ChIP–exo technology discussed in this Review.

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Glossary

Nucleosome-free region

(NFR). A region of DNA that is constitutively nucleosome-free, such as promoter regions.

Nucleosome-depleted region

(NDR). A region of DNA that has regulated nucleosome occupancy.

Dyad

The midpoint of a canonical nucleosome, which creates mirrored pseudosymmetry.

SNAP-tag

An artificially engineered enzyme capable of covalently adding any compatible epitope on demand.

Super enhancers

Regions of the genome where clusters of enhancers are located.

CpG-rich islands

A dinucleotide combination of 5′-CG-3′. Prevalent and often methylated in mammalian promoter regions.

General regulatory factors

(GRFs). DNA-binding proteins known to regulate and assist directly and indirectly in the positioning of nucleosomes.

HAND-SANT-SLIDE domain

The protein domain of the imitation SWI (ISWI) family involved in DNA translocation around a nucleosome.

Fluorescence resonance energy transfer

(FRET). A biophysical assay able to determine close (that is, nanometre scale) proximity of molecules in vivo or in vitro.

Pre-initiation complex

The complex of general transcription factor proteins assembled at transcription start sites.

MCM helicase

(Mini-chromosome maintenance helicase). A DNA helicase protein complex responsible for unwinding of the DNA helix during replication.

Autonomous replicating sequence

(ARS). A DNA sequence that allows a plasmid to replicate in Saccharomyces cerevisiae. It is often bound by origin of replication complex proteins.

ARS consensus sequences

(ACSs). Consensus DNA motifs found in ARS.

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Lai, W., Pugh, B. Understanding nucleosome dynamics and their links to gene expression and DNA replication. Nat Rev Mol Cell Biol 18, 548–562 (2017). https://doi.org/10.1038/nrm.2017.47

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