Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing

Science. 2016 Oct 28;354(6311):468-472. doi: 10.1126/science.aae0047. Epub 2016 Aug 4.

Abstract

The Xist long noncoding RNA orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional (3D) structure of the X chromosome. Yet, it remains unclear whether these changes in nuclear structure are mediated by Xist and whether they are required for silencing. Here, we show that Xist directly interacts with the Lamin B receptor, an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing by recruiting the inactive X to the nuclear lamina and by doing so enables Xist to spread to actively transcribed genes across the X. Our results demonstrate that lamina recruitment changes the 3D structure of DNA, enabling Xist and its silencing proteins to spread across the X to silence transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Female
  • Gene Silencing*
  • Lamin B Receptor
  • Mice
  • Nuclear Lamina / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • X Chromosome / metabolism*
  • X Chromosome Inactivation / genetics*

Substances

  • RNA, Long Noncoding
  • Receptors, Cytoplasmic and Nuclear
  • XIST non-coding RNA