PuSH - Publication Server of Helmholtz Zentrum München: Atrx promotes heterochromatin formation at retrotransposons.

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Sadic, D.* ; Schmidt, K.* ; Groh, S.* ; Kondofersky, I. ; Ellwart, J.W. ; Fuchs, C. ; Theis, F.J. ; Schotta, G.*

Atrx promotes heterochromatin formation at retrotransposons.

EMBO Rep. 16, 836-850 (2015)

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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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