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EMBO Rep. 2015 Jul;16(7):836-50. doi: 10.15252/embr.201439937. Epub 2015 May 26.

Atrx promotes heterochromatin formation at retrotransposons.

Author information

1
Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany.
2
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Computational Biology, Neuherberg, Germany Center for Mathematics, Chair of Mathematical Modeling of Biological Systems, Technische Universität München, Garching, Germany.
3
Helmholtz Zentrum München, Institute of Molecular Immunology, Munich, Germany.
4
Adolf-Butenandt-Institute, Ludwig Maximilians University and Munich Center for Integrated Protein Science (CiPS), Munich, Germany gunnar.schotta@med.uni-muenchen.de.

Abstract

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.

KEYWORDS:

Atrx; Daxx; IAP retrotransposons; heterochromatin; histone H3.3

PMID:
26012739
PMCID:
PMC4515123
DOI:
10.15252/embr.201439937
[Indexed for MEDLINE]
Free PMC Article

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