More than 50% of mammalian genomes consist of retrotransposon sequences. Silencing of retrotransposons by heterochromatin is essential to ensure genomic stability and transcriptional integrity. Here, we identified a short sequence element in intracisternal A particle (IAP) retrotransposons that is sufficient to trigger heterochromatin formation. We used this sequence in a genome-wide shRNA screen and identified the chromatin remodeler Atrx as a novel regulator of IAP silencing. Atrx binds to IAP elements and is necessary for efficient heterochromatin formation. In addition, Atrx facilitates a robust and largely inaccessible heterochromatin structure as Atrx knockout cells display increased chromatin accessibility at retrotransposons and non-repetitive heterochromatic loci. In summary, we demonstrate a direct role of Atrx in the establishment and robust maintenance of heterochromatin.
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Icb_biostatisticsIcb_Latent Causes
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PublikationstypArtikel: Journalartikel
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SchlagwörterAtrx ; Daxx ; Iap Retrotransposons ; Heterochromatin ; Histone H3.3; Embryonic Stem-cells; Dna Methylation; Endogenous Retroviruses; Mental-retardation; Histone Chaperone; Repressor Domain; Protein Daxx; X Syndrome; Tif1 Beta; Chromatin