Key Points
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Pericentric heterochromatin is found juxtaposed to the centromere, and is a region of chromatin that remains condensed throughout the cell cycle. Its maintenance is thought to be essential for correct chromosome segregation.
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At the molecular level, a prominent mark of pericentric heterochromatin is its enrichment in heterochromatin protein-1 (HP1). The multipartite organization of HP1 enables it to bind to numerous nuclear proteins. Among these proteins, those that are potentially involved in the stability of the higher-order structure of pericentric heterochromatin are highlighted. In this way, how HP1 proteins might participate in promoting the self perpetuation of the nuclear domain to which they belong is illustrated.
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In addition to HP1, epigenetic parameters that are key to the stability of pericentric heterochromatin in mouse are histone-H3 methylated at lysine 9 (H3-K9), hypoacetylated histones, H3-K9 methyltransferase Suv39h and an RNA component. Consistent with this idea, a key aspect in the stability of pericentric heterochromatin is therefore the inter-relationship between these various components. We propose that a local enrichment of HP1 can be achieved by the numerous binding partners that individually have a relatively low affinity.
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The nature of the interaction of HP1 with its partners within the pericentric heterochromatin domain is highly dynamic, and the properties of HP1 can be integrated into a model for the stable inheritance of the pericentric heterochromatin structure during DNA replication.
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Finally, exciting recent discoveries implicate RNA in pericentric chromatin maintenance. We compare pericentric heterochromatin in mouse cells and in Schizosaccharomyces pombe and discuss the respective functions of RNA in these regions. An unknown RNA component is required for the maintenance of the mouse pericentric heterochromatin organization, and in S. pombe the RNA-interference machinery is required for the formation of heterochromatin at centromeres.
Abstract
Heterochromatin maintenance is crucial for the clonal inheritance of cell identity, to ensure the proper segregation of chromosomes and the regulation of gene expression. Although it is architecturally stable, heterochromatin has to be flexible to cope with disrupting events such as replication. Recent progress has shed light on the paradoxical properties of heterochromatin in the nucleus, and highlights the roles of heterochromatin protein-1 and, more unexpectedly, RNA molecules in heterochromatin maintenance.
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Acknowledgements
We thank E. Heard for discussions and her helpful comments on the review, and R. Martienssen for his comments on the figures. The team of G.A. is supported by grants from Programme Collaboratif Institut Curie/Commissariat à l'Energie Atomique, la Ligue Nationale contre le Cancer (Equipe labellisée la Ligue), Euratom, the Commissariat à l'Energie Atomique and the Research Training Network (RTN).
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Glossary
- EUCHROMATIN
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A form of chromatin that is de-condensed during interphase.
- KINETOCHORE
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A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.
- CHROMOCENTRE
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Aggregates of centromere from different chromosomes.
- PERICENTRIC HETEROCHROMATIN
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A region of chromatin that is found juxtaposed to the centromere and that remains condensed throughout the cell cycle. It is considered to be typical constitutive heterochromatin.
- SATELLITE REPEAT
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A specific DNA sequence that is repeated many times in a long tandem array.
- POSITION-EFFECT VARIEGATION
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The heritable suppression of genes that results from their abnormal translocation to a position close to heterochromatin.
- CHROMODOMAIN
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A highly conserved protein-sequence motif that is common to many chromosomal proteins. In HP1 it is crucial for the interaction with histone H3 that is methylated at lysine 9.
- CHROMOSHADOW DOMAIN
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A protein-sequence motif that is related to the chromodomain in its amino-acid sequence and has so far only been found in the HP1 family of proteins.
- HISTONE-CODE HYPOTHESIS
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A hypothesis that proposes that distinct histone modifications, on one or more tails, function sequentially, or in combination, to define a code that is translated by effector proteins with specific biological functions.
- DOSAGE COMPENSATION
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A process by which the expression of sex-linked genes is equalized in species in which males and females differ in the number of sex chromosomes. In Drosophila melanogaster dosage compensation is achieved by hypertranscription of the single male X chromosome.
- X INACTIVATION
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A process by which dosage compensation in mammals is achieved by the transcriptional silencing of one of the X chromosomes in XX females.
- RNA INTERFERENCE
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(RNAi). A post-transcriptional gene-silencing process in which double-stranded RNA triggers the degradation of homologous mRNA.
- ARGONAUTE
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A family of proteins that are characterized by the presence of two homology domains (PAZ and PIWI) that are essential for the production or function of small interfering RNAs. So far, their biochemical function has not been characterized.
- DICER
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An RNaseIII-type nuclease that is required for the processing of double-stranded-RNA precursors into small interfering RNAs.
- RNA-DEPENDENT RNA POLYMERASE
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(Rdp1). An unusual RNA polymerase that uses small interfering RNAs as primers to generate long double-stranded RNA, which in turn can be processed by Dicer.
- SMALL INTERFERING RNA
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(siRNA). During RNA interference, these non-coding RNAs (around 22 nucleotides long) are derived from the processing of long double-stranded RNA. They direct the destruction of mRNA targets that have the same sequence.
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Maison, C., Almouzni, G. HP1 and the dynamics of heterochromatin maintenance. Nat Rev Mol Cell Biol 5, 296–305 (2004). https://doi.org/10.1038/nrm1355
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DOI: https://doi.org/10.1038/nrm1355
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