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  • Review Article
  • Published:

Heterochromatin revisited

Nature Reviews Genetics volume 8, pages 35–46 (2007)Cite this article

Key Points

  • Heterochromatin is a DNA-packaging state that is commonly associated with transcriptional silencing and repression of recombination.

  • Methylation of histone H3 at lysine 9 (H3K9me) and recruitment of heterochromatin protein HP1 are essential steps in heterochromatin assembly. These factors, when targeted to specific sites on chromosomes, can spread, allowing large heterochromatic domains to form.

  • Heterochromatin formation can be initiated by proteins that bind to DNA 'silencer' sequences. It can also be triggered by repetitive DNA elements through the action of the RNAi pathway.

  • Heterochromatin factors serve as a platform to recruit and facilitate the spreading of effector proteins, allowing them to exert regional control.

  • Heterochromatin mediates the spreading of RNAi machinery from nucleation sites to surrounding sequences. Chromosome-bound RNAi 'factories' might selectively produce small interfering RNAs (siRNAs), which are involved in genomic silencing and defense against parasitic elements.

  • Recruitment of histone deacetylases (HDACs) enforces the transcriptional-silencing role of heterochromatin. HDACs seem to have a crucial role in chromatin condensation.

  • Despite the well-described roles of heterochromatin in chromatin compaction and silencing, in some instances, effectors that are recruited by heterochromatin might also facilitate transcription.

  • The heterochromatin platform is dynamic and can be readily altered in response to developmental signals.

  • Boundary elements that limit the spread of heterochromatin have been described in some systems. They seem to work by diverse mechanisms.

Abstract

The formation of heterochromatin, which requires methylation of histone H3 at lysine 9 and the subsequent recruitment of chromodomain proteins such as heterochromatin protein HP1, serves as a model for the role of histone modifications and chromatin assembly in epigenetic control of the genome. Recent studies in Schizosaccharomyces pombe indicate that heterochromatin serves as a dynamic platform to recruit and spread a myriad of regulatory proteins across extended domains to control various chromosomal processes, including transcription, chromosome segregation and long-range chromatin interactions.

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Figure 1: Mechanisms for the initiation of heterochromatin assembly.
Figure 2: RNAi-mediated heterochromatin assembly and silencing in fission yeast.
Figure 3: Heterochromatin as a platform for the recruitment of effectors across extended domains.
Figure 4: Heterochromatin recruits both silencing and anti-silencing factors.
Figure 5: A model for a possible role for small RNAs in genome organization.
Figure 6: Heterochromatin regulates cell-type specific spreading of a protein complex.

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Acknowledgements

We thank J. Sabl for her help in editing the manuscript, and H. Cam, M. Lichten and anonymous reviewers for helpful comments. We apologize to colleagues whose work could not be cited due to space limitations. Research in the Grewal laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, USA.

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  1. Laboratory of Molecular Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Shiv I. S. Grewal & Songtao Jia

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  1. Shiv I. S. Grewal
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Correspondence to Shiv I. S. Grewal.

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Glossary

Knobs

Blocks of heterochromatin other than the centromeres and nucleolar organizer regions.

Co-optation

The adaptation of an existing biological feature for a new purpose.

Spindle

A eukaryotic cytoskeletal structure that is made of bundles of microtubules and functions to segregate chromosomes to the daughter cells during mitosis and meiosis.

Conjugation

A process of sexual reproduction in certain algae and fungi in which temporary or permanent fusion occurs, resulting in the union of the male and female gametes.

Meiotic drive

A process that causes some alleles to be overrepresented in the gametes that are formed during meiosis.

Paramutation

An interaction between two alleles of a single locus, resulting in a heritable change in the expression of one allele, which is induced by the other allele.

Imprinting

The epigenetic marking of a gene on the basis of parental origin, which results in monoallelic expression.

RNAi

A mechanism by which dsRNA triggers the destruction of cognate mRNA.

Dicer

An RNase III nuclease that processes dsRNA precursors into small interfering RNAs.

Argonaute proteins

PAZ- and PIWI-domain-containing proteins that are essential components of RNAi effector complexes, which bind small interfering RNAs.

RNA-dependent RNA polymerase

An RNA polymerase that generates dsRNAs from ssRNAs to strengthen the RNAi response.

siRNA

Small interfering RNAs (∼22–24 nucleotides), which are derived from the processing of long dsRNA by Dicer.

Polytene chromosomes

Chromosomes produced by multiple rounds of replication that remain synapsed together.

Kinetochore

A multiprotein structure that is assembled on centromeric DNA to mediate the attachment and movement of chromosomes along the mitotic spindle.

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Grewal, S., Jia, S. Heterochromatin revisited. Nat Rev Genet 8, 35–46 (2007). https://doi.org/10.1038/nrg2008

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