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Histone variants — ancient wrap artists of the epigenome
Nature Reviews Molecular Cell Biologyvolume 11, pages264–275 (2010)Cite this article
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Key Points
Canonical histones H2A, H2B, H3 and H4 wrap DNA to form nucleosome particles that compact the genome. Histone variants have diverse additional roles in chromosome metabolism and can differ from canonical histones in stability, DNA wrapping and specialized domains.
The 'universal' variants, centromeric histone variant H3 (CenH3), H3.3, H2A.Z and H2A.X, appeared before the divergence of modern eukaryotes and function in common eukaryotic cellular processes such as histone replacement, chromosome segregation, DNA repair, and transcriptional regulation. Specialized histones have arisen in some lineages to perform additional tasks.
Centromeric nucleosomes contain CenH3 and form the essential foundation of the kinetochore. The subunit composition of the CenH3 histone core has been the subject of lively debate and it has been found to wrap DNA in a right-handed direction, opposite to that of ordinary nucleosomes.
H2A.Z has a conserved role in transcription initiation that might be descended from a hypothetical ancient mode of gene regulation by histone variants found in modern trypanosomes. Dynamic cellular processes might dramatically alter the stability of H2A.Z nucleosomes and thereby facilitate transcription initiation.
Chromatin must be remodelled in processes such as DNA repair and sex chromosome silencing. Variants H2A.X and H3.3 have prominent roles in remodelling, with specialized sperm histones and protamines mediating sperm packaging and decondensation.
Lineage-specific H2A variants have diverse carboxy-terminal tails that can wrap more DNA with additional oligopeptide motifs, or less DNA with a shorter docking domain. They sometimes have non-histone domains, which in macroH2As inhibit polyADP-ribosylation and contribute to conditional gene silencing.
Abstract
Histones wrap DNA to form nucleosome particles that compact eukaryotic genomes. Variant histones have evolved crucial roles in chromosome segregation, transcriptional regulation, DNA repair, sperm packaging and other processes. 'Universal' histone variants emerged early in eukaryotic evolution and were later displaced for bulk packaging roles by the canonical histones (H2A, H2B, H3 and H4), the synthesis of which is coupled to DNA replication. Further specializations of histone variants have evolved in some lineages to perform additional tasks. Differences among histone variants in their stability, DNA wrapping, specialized domains that regulate access to DNA, and post-translational modifications, underlie the diverse functions that histones have acquired in evolution.
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Acknowledgements
We thank our colleagues for stimulating discussions and anonymous reviewers for their helpful comments. Our work has been funded by the Howard Hughes Medical Institute.
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Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109-1024, Washington, USA
Paul B. Talbert & Steven Henikoff
Paul B. Talbert & Steven Henikoff
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Glossary
- Histone chaperone
An escort protein that performs a transfer reaction on a histone, such as deposition onto DNA, eviction from DNA, transfer to another chaperone or enzyme, or storage for later use.
- Supercoil
A contortion in DNA that occurs as a consequence to over- or under-twisting of the DNA helix. Supercoils can be introduced during DNA packaging and DNA–RNA synthesis. Topoisomerases sense supercoiling and can either generate or dissipate it by changing DNA topology.
- Centromere
The region of a chromosome that is attached to the spindle during nuclear division.
- Kinetochore
A large multiprotein complex that assembles onto the centromere of the chromosome and links it to the microtubules of the mitotic spindle. The kinetochore is also a signalling centre for many of the proteins that control the progression of mitosis.
- Epigenetic memory
An effect on gene expression or function that is not a result of DNA sequence changes and is heritable through cell division.
- Nuclease-hypersensitive site
A chromosomal site that shows increased sensitivity to nucleases such as DNase I and that are correlated to regions of reduced nucleosome density and gene regulatory sites.
- Heterochromatin
A highly condensed form of chromatin with very low transcriptional activity. It occurs at defined sites, such as around centromeres or telomeres. Typically it is composed of repetitive sequences and transposons, with few genes present.
- Homeobox gene
One of a family of genes that encode homeodomain-containing transcription factors, which are involved in the patterning of the body during development.
- Protamine
A small, highly basic protein that tightly packages sperm DNA, replacing histones completely or to varying degrees in many animals.
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Talbert, P., Henikoff, S. Histone variants — ancient wrap artists of the epigenome.Nat Rev Mol Cell Biol11, 264–275 (2010). https://doi.org/10.1038/nrm2861
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