title: Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing.
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.
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Chun-Kan
authors: CK
authors: Chen
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Mario
authors: M
authors: Blanco
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Constanza
authors: C
authors: Jackson
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Erik
authors: E
authors: Aznauryan
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Noah
authors: N
authors: Ollikainen
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Christine
authors: C
authors: Surka
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors: Amy
authors: A
authors: Chow
authors: European Molecular Biology Laboratory-Monterotondo, Via Ramarini 32, 00015 Monterotondo (RM), Italy.
authors: Andrea
authors: A
authors: Cerase
authors: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors: Patrick
authors: P
authors: McDonel
authors: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. mguttman@caltech.edu.
authors: Mitchell
authors: M
authors: Guttman
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D020868:Gene Silencing; D051379:Mice; D034881:Nuclear Lamina / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014960:X Chromosome / Q000378:metabolism*; D049951:X Chromosome Inactivation / Q000235:genetics*; D000097682:Lamin B Receptor
chemical_list: D062085:RNA, Long Noncoding; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor; C077885:XIST non-coding RNA