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Cell. 2014 Nov 6;159(4):869-83. doi: 10.1016/j.cell.2014.10.019.

ATRX directs binding of PRC2 to Xist RNA and Polycomb targets.

Author information

1
Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA USA.
2
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA USA.
3
Department of Bioengineering, Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA USA.
4
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA.
5
Howard Hughes Medical Institute; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA USA; Department of Genetics, Harvard Medical School, Boston, MA USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA USA. Electronic address: lee@molbio.mgh.harvard.edu.

Erratum in

  • Cell. 2015 Jan 29;160(3):568-9.
  • Cell. 2014 Nov 20;159(5):1228.

Abstract

X chromosome inactivation (XCI) depends on the long noncoding RNA Xist and its recruitment of Polycomb Repressive Complex 2 (PRC2). PRC2 is also targeted to other sites throughout the genome to effect transcriptional repression. Using XCI as a model, we apply an unbiased proteomics approach to isolate Xist and PRC2 regulators and identified ATRX. ATRX unexpectedly functions as a high-affinity RNA-binding protein that directly interacts with RepA/Xist RNA to promote loading of PRC2 in vivo. Without ATRX, PRC2 cannot load onto Xist RNA nor spread in cis along the X chromosome. Moreover, epigenomic profiling reveals that genome-wide targeting of PRC2 depends on ATRX, as loss of ATRX leads to spatial redistribution of PRC2 and derepression of Polycomb responsive genes. Thus, ATRX is a required specificity determinant for PRC2 targeting and function.

PMID:
25417162
PMCID:
PMC4379047
DOI:
10.1016/j.cell.2014.10.019
[Indexed for MEDLINE]
Free PMC Article

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