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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Public Library of Science (PLoS)
2010-05-01
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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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language | English |
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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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