ATRX Directs Binding of PRC2 to Xist RNA and Polycomb Targets
Name
ATRX Directs.pdf
Size
2.85 MB
Format
Adobe PDF
Checksum (MD5)
227f4c191b4f924a1a33eae23f9c7930
Author(s)
Sarma, Kavitha
Cifuentes-Rojas, Catherine
Ergun, Ayla
Jeon, Yesu
Sadreyev, Ruslan
Lee, Jeannie T.
White, Forest M.
Del Rosario, Amanda M
Date Issued
November 2014
Journal
Cell
Publisher
Elsevier
Citation
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.
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2014.10.019
