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Histone chaperone networks shaping chromatin function

Nature Reviews Molecular Cell Biology volume 18, pages 141–158 (2017)Cite this article

Subjects

Key Points

  • Chromatin integrity and functionality is governed by the controlled assembly and disassembly of nucleosomes.

  • An elaborate histone chaperone network governs histone provision, chromatin assembly, histone recycling and histone turnover.

  • Histone chaperone networks operate through histone-dependent co-chaperone interactions and direct chaperone–chaperone contacts.

  • The mode of action of histone chaperones is interpreted from structural and biochemical studies of histone–chaperone complexes.

  • Key molecular functions of histone chaperones include the shielding of functional histone interfaces and trapping histones in non-nucleosomal conformations.

  • The integration of histone chaperone function across DNA metabolic processes acts to maintain genome and epigenome integrity.

Abstract

The association of histones with specific chaperone complexes is important for their folding, oligomerization, post-translational modification, nuclear import, stability, assembly and genomic localization. In this way, the chaperoning of soluble histones is a key determinant of histone availability and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified histones evicted from chromatin.

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Figure 1: Overview of histone deposition mechanisms.
Figure 2: Structural features of histone–chaperone complexes.
Figure 3: Other histone chaperone structures.
Figure 4: The histone supply network.
Figure 5: Recruitment of histone chaperones to chromatin.
Figure 6: Parental histone recycling during DNA replication.

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Acknowledgements

The authors apologize for the many studies in the histone chaperone field that were unable to be cited owing to space restrictions. The authors thank C. Alabert, A. Bowman and Z. Jasencakova for useful comments on the manuscript and for help with figure design. D.J.P. is supported by funds from the Leukemia and Lymphoma Society and STARR Foundation and by the Memorial Sloan-Kettering Cancer Core Grant (P30 CA008748). A.G. is an EMBO Young Investigator and her research is supported by the European Research Council (ERC StG, no. 281765), the Danish National Research Foundation to the Center for Epigenetics (DNRF82), the Danish Cancer Society, the Danish Medical Research Council, the Novo Nordisk Foundation and the Lundbeck Foundation.

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Author notes

  1. Colin M. Hammond and Caroline B. Strømme: These authors contributed equally to this work.

Authors and Affiliations

  1. Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark

    Colin M. Hammond, Caroline B. Strømme & Anja Groth

  2. Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA

    Hongda Huang & Dinshaw J. Patel

Authors
  1. Colin M. Hammond
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  2. Caroline B. Strømme
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  3. Hongda Huang
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  4. Dinshaw J. Patel
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  5. Anja Groth
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Correspondence to Anja Groth.

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Competing interests

The authors declare competing financial interests: C.M.H., H.H., D.J.P. and A.G. are named inventors on a patent application covering the discoveries in Saredi et al. H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex. Nature 534, 714–718 (2016).

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DATABASES

RSCB Protein Data Bank

SGD YeastMine

Glossary

Histone chaperones

Defined here as proteins that handle non-nucleosomal histones in vivo and mediate the assembly of nucleosomes from isolated histones and DNA in vitro.

Histone storage

The sequestration of histones in the soluble fraction of the cell that prevents their degradation.

Histone turnover

The eviction of nucleosomal histones, followed by deposition of new histones at the same genomic loci.

Histone chaperone network

The integration of histone chaperone functions to support histone dynamics across various cellular processes.

Canonical histones

Core histone subtypes (H3.1, H3.2, H4, H2A and H2B) that are expressed in S phase of the cell cycle and mainly incorporated into nucleosomes in a DNA replication-dependent manner.

Replacement variants

Histone subtypes (such as H3.3, CENP-A, and H2A.Z) incorporated into nucleosomes via DNA replication-independent pathways and for which expression is not restricted to S phase.

De novo histone deposition

Incorporation of newly synthesized histones into chromatin.

Co-chaperone

Here defined as a complex containing two or more histone chaperones brought together in a histone-dependent manner.

Epigenetic plasticity

Heritable information other than DNA sequence that maintains cellular traits while also being subject to change without said changes being permanent.

H3K56ac

A mark of newly synthesized H3–H4 in yeast, catalysed by Rtt109 in an Asf1-dependent manner, that promotes replication-dependent histone deposition.

Histone recycling

Re-deposition of histones evicted from chromatin by cellular processes that require access to the DNA template.

Dyad DNA

The dyad position locates the pseudo axis of symmetry, which coincides with the central base pair (or pairs) of nucleosomal DNA and the H3–H4 tetramerization interface, around which the nucleosome can be rotated 180° and map back onto itself.

Tetrasome

Thought to be the first assembly intermediate during nucleosome assembly, the tetrasome is the product of the deposition of a H3–H4 tetramer on DNA.

RBAP46 and RBAP48

Histone chaperone homologues that are almost identical and seem to be interchangeable in most of their chromatin-modifying complexes, apart from HAT1 (RBAP46) and CAF1 (RBAP48).

Histone reader

A protein that binds to histones in a post-translational modification-dependent manner.

H4K20me0

Histone H4 unmethylated at lysine 20 (H4K20me0); a signature of newly synthesized histones that marks post-replicative chromatin until G2/M phase of the cell cycle, when H4K20 methylation is established on those new histones.

Soluble histones

Non-nucleosomal histones.

H4K5acK12ac

Highly conserved diacetylation mark, catalysed by RBAP46–HAT1, that marks newly synthesized histone H4 before deposition.

Histone exchange

The replacement of nucleosomal histones with the corresponding canonical histones (H2A–H2B, H3–H4) or replacement variants (H2A.Z–H2B, H3.3–H4).

Hexasome

A nucleosome intermediate generated by either the loss of one H2A–H2B dimer from the nucleosome or the addition of one H2A–H2B dimer to the H3–H4 tetrasome.

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Hammond, C., Strømme, C., Huang, H. et al. Histone chaperone networks shaping chromatin function. Nat Rev Mol Cell Biol 18, 141–158 (2017). https://doi.org/10.1038/nrm.2016.159

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