| Abstract: |
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. © 2010 Gou et al. |
| Keywords: |
controlled study; unclassified drug; genetics; nonhuman; binding affinity; protein function; protein motif; nonhistone protein; animal cell; animal; metabolism; mammalia; animals; chromosomal proteins, non-histone; animal tissue; gene targeting; protein dna binding; protein protein interaction; protein binding; embryo development; gene function; dna methylation; cell type; vertebrata; animal embryo; prenatal development; embryo, nonmammalian; chemistry; histone; histone h3; protein structure, tertiary; drosophila melanogaster; gene silencing; dna methyltransferase; retinoblastoma protein; drosophila proteins; histones; protein tertiary structure; lysine; dna (cytosine 5) methyltransferase; dna (cytosine-5-)-methyltransferase; protein methylation; heterochromatin; drosophila protein; imaginal disc; eye; eye development; regulatory sequences, nucleic acid; regulatory sequence; dna methyltransferase 2; heterochromatin protein 1; nucleic acid binding protein; setdb1 protein; heterochromatin specific nonhistone chromosomal protein hp 1; heterochromatin-specific nonhistone chromosomal protein hp-1; mt2 protein, drosophila; setdb1 protein, drosophila; insect cell; insect development; retroposon; arthropoda; chordata; retroelements
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