DOI: 10.1101/gad.300704. A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin

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

10.1101/gad.300704

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

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.

Bibliography

Schotta, G., Lachner, M., Sarma, K., Ebert, A., Sengupta, R., Reuter, G., Reinberg, D., & Jenuwein, T. (2004). A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin. Genes & Development, 18(11), 1251â1262.

Authors 8

Gunnar Schotta (first)
Monika Lachner (additional)
Kavitha Sarma (additional)
Anja Ebert (additional)
Roopsha Sengupta (additional)
Gunter Reuter (additional)
Danny Reinberg (additional)
Thomas Jenuwein (additional)

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Dates

Type	When
Created	21 years, 3 months ago (May 17, 2004, 8:53 p.m.)
Deposited	3 years, 9 months ago (Nov. 16, 2021, 10:17 a.m.)
Indexed	31 minutes ago (Sept. 3, 2025, 3:07 a.m.)
Issued	21 years, 3 months ago (May 14, 2004)
Published	21 years, 3 months ago (May 14, 2004)
Published Online	21 years, 3 months ago (May 14, 2004)
Published Print	21 years, 3 months ago (June 1, 2004)

Funders 0

None

BibTeX

@article{Schotta_2004, title={A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin}, volume={18}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.300704}, DOI={10.1101/gad.300704}, number={11}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Schotta, Gunnar and Lachner, Monika and Sarma, Kavitha and Ebert, Anja and Sengupta, Roopsha and Reuter, Gunter and Reinberg, Danny and Jenuwein, Thomas}, year={2004}, month=may, pages={1251–1262} }

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