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A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin

Schotta, Gunnar, Lachner, Monika, Sarma, Kavitha, Ebert, Anja, Sengupta, Roopsha, Reuter, Gunter, Reinberg, Danny, Jenuwein, Thomas·2004·Genes & Development
DOI 10.1101/gad.300704
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Abstract

Histone lysine methylation is a central modification to mark functionally distinct chromatin regions. In particular, H3-K9 trimethylation has emerged as a hallmark of pericentric heterochromatin in mammals. Here we show that H4-K20 trimethylation is also focally enriched at pericentric heterochromatin. Intriguingly, H3-K9 trimethylation by the Suv39h HMTases is required for the induction of H4-K20 trimethylation, although the H4 Lys 20 position is not an intrinsic substrate for these enzymes. By using a candidate approach, we identified Suv4-20h1 and Suv4-20h2 as two novel SET domain HMTases that localize to pericentric heterochromatin and specifically act as nucleosomal H4-K20 trimethylating enzymes. Interaction of the Suv4-20h enzymes with HP1 isoforms suggests a sequential mechanism to establish H3-K9 and H4-K20 trimethylation at pericentric heterochromatin. Heterochromatic H4-K20 trimethylation is evolutionarily conserved, and in Drosophila , the Suv4-20 homolog is a novel PEV modifier to regulate position-effect variegation. Together, our data indicate a function for H4-K20 trimethylation in gene silencing and further suggest H3-K9 and H4-K20 trimethylation as important components of a repressive pathway that can index pericentric heterochromatin.

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  • Heterochromatin assembly at pericentric regions requires trimethylation of histones H3K9 and H4K20, as well as HP1α binding, and is important for chromosomal stability.

    “In particular, heterochromatin assembly at pericentric regions requires trimethylation of histones H3K9 and H4K20, as well as HP1α binding, and is important for chromosomal stability (Schotta et al., 2004).”

    From The Hallmarks of Aging (2013) · cites this paper as Schotta et al., 2004

    The sections on pericentric heterochromatin and HP1 interactions report enrichment of both trimethylation marks and propose a sequential pathway involving HP1α and HP1β. The paper calls that assembly pathway a tentative model, rather than demonstrating that all three components are required. In “Suv4-20h enzymes are novel Su(var) genes” (page unavailable), it identifies protection of genome stability as a function of heterochromatin, while describing H4-K20 trimethylation’s participation as a prediction. (LLM, conf=0.86)

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Metadata

Authors
Schotta, G., Lachner, M., Sarma, K., Ebert, A., Sengupta, R., Reuter, G., Reinberg, D., & Jenuwein, T.
Venue
Genes & Development
Publisher
Cold Spring Harbor Laboratory
Published
2004-05-14
Volume
18
Issue
11
Pages
1251-1262
ISSN
  • 0890-9369
  • 1549-5477
DOI
10.1101/gad.300704
Cited by
1,031
References
5
Language
en

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