ATRX Directs Binding of PRC2 to Xist RNA and Polycomb Targets
Author(s)Sarma, Kavitha; Cifuentes-Rojas, Catherine; Ergun, Ayla; Jeon, Yesu; Sadreyev, Ruslan; Lee, Jeannie T.; Del Rosario, Amanda M.; White, Forest M.; ... Show more Show less
MetadataShow full item record
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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Biological Engineering
Sarma, Kavitha, Catherine Cifuentes-Rojas, Ayla Ergun, Amanda del Rosario, Yesu Jeon, Forest White, Ruslan Sadreyev, and Jeannie T. Lee. “ATRX Directs Binding of PRC2 to Xist RNA and Polycomb Targets.” Cell 159, no. 4 (November 2014): 869–883.
Author's final manuscript