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

被引:193
|
作者
Chen, Chun-Kan [1 ]
Blanco, Mario [1 ]
Jackson, Constanza [1 ]
Aznauryan, Erik [1 ]
Ollikainen, Noah [1 ]
Surka, Christine [1 ]
Chow, Amy [1 ]
Cerase, Andrea [2 ]
McDonel, Patrick [3 ]
Guttman, Mitchell [1 ]
机构
[1] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA
[2] European Mol Biol Lab Monterotondo, Via Ramarini 32, I-00015 Monterotondo, RM, Italy
[3] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01655 USA
关键词
FACULTATIVE HETEROCHROMATIN; RNA; INACTIVATION; GENOME; CELLS; LOCALIZATION; MOTION; GENES;
D O I
10.1126/science.aae0047
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:468 / 472
页数:6
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