SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.

DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patte...

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Main Authors: Dawei Gou, Monica Rubalcava, Silvia Sauer, Felipe Mora-Bermúdez, Hediye Erdjument-Bromage, Paul Tempst, Elisabeth Kremmer, Frank Sauer
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-05-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2871795?pdf=render
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author Dawei Gou
Monica Rubalcava
Silvia Sauer
Felipe Mora-Bermúdez
Hediye Erdjument-Bromage
Paul Tempst
Elisabeth Kremmer
Frank Sauer
author_facet Dawei Gou
Monica Rubalcava
Silvia Sauer
Felipe Mora-Bermúdez
Hediye Erdjument-Bromage
Paul Tempst
Elisabeth Kremmer
Frank Sauer
author_sort Dawei Gou
collection DOAJ
description DNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9) by members of the Su(var)3-9 family of histone methyltransferases (HMTs) triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1) can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2) and Su(var)205, the Drosophila ortholog of mammalian "Heterochromatin Protein 1", to target genes for dSETDB1. By enlisting Dnmt2 and Su(var)205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb) in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development.
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spelling doaj.art-2452cc1d8bf644ee833dcc7473a509d22022-12-22T01:56:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1058110.1371/journal.pone.0010581SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.Dawei GouMonica RubalcavaSilvia SauerFelipe Mora-BermúdezHediye Erdjument-BromagePaul TempstElisabeth KremmerFrank SauerDNA methylation is fundamental for the stability and activity of genomes. Drosophila melanogaster and vertebrates establish a global DNA methylation pattern of their genome during early embryogenesis. Large-scale analyses of DNA methylation patterns have uncovered revealed that DNA methylation patterns are dynamic rather than static and change in a gene-specific fashion during development and in diseased cells. However, the factors and mechanisms involved in dynamic, postembryonic DNA methylation remain unclear. Methylation of lysine 9 in histone H3 (H3-K9) by members of the Su(var)3-9 family of histone methyltransferases (HMTs) triggers embryonic DNA methylation in Arthropods and Chordates. Here, we demonstrate that Drosophila SETDB1 (dSETDB1) can mediate DNA methylation and silencing of genes and retrotransposons. We found that dSETDB1 tri-methylates H3-K9 and binds methylated CpA motifs. Tri-methylation of H3-K9 by dSETDB1 mediates recruitment of DNA methyltransferase 2 (Dnmt2) and Su(var)205, the Drosophila ortholog of mammalian "Heterochromatin Protein 1", to target genes for dSETDB1. By enlisting Dnmt2 and Su(var)205, dSETDB1 triggers DNA methylation and silencing of genes and retrotransposons in Drosophila cells. DSETDB1 is involved in postembryonic DNA methylation and silencing of Rt1b{} retrotransposons and the tumor suppressor gene retinoblastoma family protein 1 (Rb) in imaginal discs. Collectively, our findings implicate dSETDB1 in postembryonic DNA methylation, provide a model for silencing of the tumor suppressor Rb, and uncover a role for cell type-specific DNA methylation in Drosophila development.http://europepmc.org/articles/PMC2871795?pdf=render
spellingShingle Dawei Gou
Monica Rubalcava
Silvia Sauer
Felipe Mora-Bermúdez
Hediye Erdjument-Bromage
Paul Tempst
Elisabeth Kremmer
Frank Sauer
SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
PLoS ONE
title SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
title_full SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
title_fullStr SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
title_full_unstemmed SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
title_short SETDB1 is involved in postembryonic DNA methylation and gene silencing in Drosophila.
title_sort setdb1 is involved in postembryonic dna methylation and gene silencing in drosophila
url http://europepmc.org/articles/PMC2871795?pdf=render
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