CaltechAUTHORS
Published October 28, 2016 | Version Supplemental Material
Journal Article Open

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

Creators

  • 1. ROR icon California Institute of Technology
  • 2. ROR icon European Molecular Biology Laboratory
  • 3. ROR icon University of Massachusetts Medical School

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.

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.

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Supplemental Material - aae0047-Chen.SM.pdf

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aae0047-Chen.SM.pdf

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Additional details

Identifiers

Eprint ID
66233
DOI
10.1126/science.aae0047
Resolver ID
CaltechAUTHORS:20160418-091128052

Related works

Describes
10.1126/science.aae0047 (DOI)
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80510 (URL)
https://guttmanlab.caltech.edu/lab-resources/data/ (URL)

Funding

NIH Predoctoral Fellowship
T32GM07616
New York Stem Cell Foundation
NIH
DP5OD012190
Edward Mallinckrodt Foundation
Sontag Foundation
Searle Scholars Program
Pew Charitable Trust
Caltech

Dates

Created
2016-08-05
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field