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

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Science  04 Aug 2016:
DOI: 10.1126/science.aae0047

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Xist orchestrates X chromosome inactivation, a process that entails chromosome-wide silencing and remodeling of the three-dimensional 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 (LBR), an integral component of the nuclear lamina, and that this interaction is required for Xist-mediated silencing. We show that this interaction recruits 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 accessibility of DNA thereby enabling Xist, and its silencing proteins, to spread across the X to silence transcription.

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