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The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome

Engreitz, Jesse M. and Pandya-Jones, Amy and McDonel, Patrick and Shishkin, Alexander and Sirokman, Klara and Surka, Christine and Kadri, Sabah and Xing, Jeffrey and Goren, Alon and Lander, Eric S. and Plath, Kathrin and Guttman, Mitchell (2013) The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome. Science, 341 (6147). Art. No. 1237973. ISSN 0036-8075. PMCID PMC3778663. https://resolver.caltech.edu/CaltechAUTHORS:20161121-141829859

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Abstract

Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.1237973DOIArticle
http://science.sciencemag.org/content/341/6147/1237973PublisherArticle
http://www.sciencemag.org/cgi/content/full/science.1237973/DC1PublisherSupplementary Materials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778663/PubMed CentralArticle
http://www.lncrna.caltech.edu/RAP/AuthorAdditional data and information
ORCID:
AuthorORCID
Guttman, Mitchell0000-0003-4748-9352
Additional Information:© 2013 American Association for the Advancement of Science. Received 18 March 2013; accepted 20 June 2013. Published online 4 July 2013. We thank A. Gnirke for initial discussions about the RAP method; T. Mikkelsen for assistance with oligonucleotide synthesis; M. Garber and J. Rinn for helpful discussions and ideas; A. Wutz for generously providing Xist transgenic cell lines; S. Rao, N. Cherniavsky, and E. Lieberman-Aiden for analytical help and discussions; P. Russell, M. Cabili, E. Hacisuleyman, and L. Goff for critical reading of the manuscript; L. Gaffney for assistance with figures; and S. Knemeyer for illustrations. Supported by the Fannie and John Hertz Foundation and National Defense Science and Engineering Graduate Fellowship (J.M.E.); an NIH postdoctoral fellowship (1F32GM103139-01) (A.P.-J.); NIH Director’s Early Independence Award DP5OD012190 (M.G.), National Human Genome Research Institute Center for Excellence for Genomic Sciences grant P50HG006193 (M.G.); National Institute of General Medical Sciences grant P01GM099134 (K.P.); California Institute for Regenerative Medicine grants RN1-00564, RB3-05080, and RB4-06133 (K.P.); the Broad Institute of MIT and Harvard (M.G. and E.S.L.); and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA (K.P.). Sequencing data are available online from the NCBI Gene Expression Omnibus (accession no. GSE46918, www.ncbi.nlm.nih.gov/geo/) and additional data and information is available at www.lncRNA.caltech.edu/RAP/. J.M.E., E.S.L., and M.G. are inventors on a patent application from the Broad Institute that covers the selective purification of RNA-bound molecular complexes in cells.
Funders:
Funding AgencyGrant Number
Fannie and John Hertz FoundationUNSPECIFIED
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
NIH Postdoctoral Fellowship1F32GM103139-01
NIHDP5OD012190
NIHP50HG006193
NIHP01GM099134
California Institute for Regenerative Medicine (CIRM)RN1-00564
California Institute for Regenerative Medicine (CIRM)RB3-05080
California Institute for Regenerative Medicine (CIRM)RB4-06133
Broad Institute of MIT and HarvardUNSPECIFIED
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell ResearchUNSPECIFIED
National Human Genome Research InstituteUNSPECIFIED
Issue or Number:6147
PubMed Central ID:PMC3778663
Record Number:CaltechAUTHORS:20161121-141829859
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20161121-141829859
Official Citation:The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome By Jesse M. Engreitz, Amy Pandya-Jones, Patrick McDonel, Alexander Shishkin, Klara Sirokman, Christine Surka, Sabah Kadri, Jeffrey Xing, Alon Goren, Eric S. Lander, Kathrin Plath, Mitchell Guttman Science 16 Aug 2013: Vol. 341, Issue 6147, DOI: 10.1126/science.1237973
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72209
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Nov 2016 23:21
Last Modified:03 Oct 2019 16:15

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