A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin
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 heterochromat...
Saved in:
Published in | Genes & development Vol. 18; no. 11; pp. 1251 - 1262 |
---|---|
Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Cold Spring Harbor Laboratory Press
01.06.2004
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.300704. These authors contributed equally to this work. Supplemental material is available at http://www.genesdev.org. Corresponding author. E-MAIL jenuwein@imp.univie.ac.at ; FAX 43-1-7987153. |
ISSN: | 0890-9369 1549-5477 |
DOI: | 10.1101/gad.300704 |