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

Chen, Chun-Kan and Blanco, Mario and Jackson, Costanza and Aznauryan, Erik and Ollikainen, Noah and Surka, Christine and Chow, Amy and Cerase, Andrea and McDonel, Patrick and Guttman, Mitchell (2016) Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science, 354 (6311). pp. 468-472. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20160418-091128052

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.aae0047DOIArticle
http://science.sciencemag.org/content/354/6311/468PublisherArticle
http://www.sciencemag.org/content/354/6311/468/suppl/DC1PublisherSupplementary Materials
http://www.lncRNA.caltech.edu/data.phpAuthorAddtional Data
ORCID:
AuthorORCID
Guttman, Mitchell0000-0003-4748-9352
Additional Information:© 2016 American Association for the Advancement of Science. 05 December 2015; accepted 25 July 2016. Published online 04 August 2016. We thank K. Plath for extensive discussions; A. Collazo for microscopy help; A. Shur, P. Quintero, and V. Grishkevich for technical help; M. Lai for analytical help; J. Engreitz, S. Quinodoz, M. Garber, I. Amit, and J. Rinn for comments on the manuscript; and S. Knemeyer for illustrations. Imaging was performed in the Biological Imaging Facility, and sequencing was performed in the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology. C.-K.C. is supported by a NIH National Research Service Award training grant (T32GM07616). This research was funded by the New York Stem Cell Foundation, a NIH Director’s Early Independence Award (DP5OD012190), the Edward Mallinckrodt Foundation, Sontag Foundation, Searle Scholars Program, Pew-Steward Scholars program, and funds from the California Institute of Technology. M.G. is a New York Stem Cell Foundation–Robertson Investigator. Sequencing data are available online from the National Center for Biotechnology Information Gene Expression Omnibus (www.ncbi.nlm.nih.gov/geo) accession no. GSE80510 (RAP data) and GSE86250 (CLIP data), and additional data and information are available at www.lncRNA.caltech.edu/data.php.
Funders:
Funding AgencyGrant Number
NIH Predoctoral FellowshipT32GM07616
New York Stem Cell FoundationUNSPECIFIED
NIHDP5OD012190
Edward Mallinckrodt FoundationUNSPECIFIED
Sontag FoundationUNSPECIFIED
Searle Scholars ProgramUNSPECIFIED
Pew Charitable TrustUNSPECIFIED
CaltechUNSPECIFIED
Record Number:CaltechAUTHORS:20160418-091128052
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20160418-091128052
Official Citation:Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing By Chun-Kan Chen, Mario Blanco, Constanza Jackson, Erik Aznauryan, Noah Ollikainen, Christine Surka, Amy Chow, Andrea Cerase, Patrick McDonel, Mitchell Guttman Science 28 Oct 2016: Vol. 354, Issue 6311, pp. 468-472 DOI: 10.1126/science.aae0047
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66233
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:05 Aug 2016 17:04
Last Modified:03 Jan 2018 19:25

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