ATRX directs binding of PRC2 to Xist RNA and Polycomb targets

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA Helicases / isolation & purification
  • DNA Helicases / metabolism*
  • Embryonic Stem Cells / metabolism
  • Female
  • Male
  • Mice
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 2 / metabolism*
  • RNA, Long Noncoding / metabolism*
  • X Chromosome Inactivation*
  • X-linked Nuclear Protein


  • Nuclear Proteins
  • RNA, Long Noncoding
  • XIST non-coding RNA
  • Polycomb Repressive Complex 2
  • DNA Helicases
  • Atrx protein, mouse
  • X-linked Nuclear Protein