4.8 Article

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

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SCIENCE
卷 354, 期 6311, 页码 468-472

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aae0047

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资金

  1. NIH National Research Service Award [T32GM07616]
  2. New York Stem Cell Foundation
  3. NIH Director's Early Independence Award [DP5OD012190]
  4. Edward Mallinckrodt Foundation
  5. Sontag Foundation
  6. Searle Scholars Program
  7. Pew-Steward Scholars program
  8. California Institute of Technology

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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.

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