Altmetric

Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming

File Description SizeFormat 
ncomms12354.pdfPublished version1.86 MBAdobe PDFDownload
Title: Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming
Author(s): Cantone, I
Bagci, H
Dormann, D
Dharmalingam, G
Nesterova, T
Brockdorff, N
Rougeulle, C
Vallot, C
Heard, E
Chaligne, R
Merkenschlager, M
Fisher, AG
Item Type: Journal Article
Abstract: Erasure of epigenetic memory is required to convert somatic cells towards pluripotency. Reactivation of the inactive X chromosome (Xi) has been used to model epigenetic reprogramming in mouse, but human studies are hampered by Xi epigenetic instability and difficulties in tracking partially reprogrammed iPSCs. Here we use cell fusion to examine the earliest events in the reprogramming-induced Xi reactivation of human female fibroblasts. We show that a rapid and widespread loss of Xi-associated H3K27me3 and XIST occurs in fused cells and precedes the bi-allelic expression of selected Xi-genes by many heterokaryons (30-50%). After cell division, RNA-FISH and RNA-seq analyses confirm that Xi reactivation remains partial and that induction of human pluripotency-specific XACT transcripts is rare (1%). These data effectively separate pre- and post-mitotic events in reprogramming-induced Xi reactivation and reveal a complex hierarchy of epigenetic changes that are required to reactivate the genes on the human Xi chromosome.
Publication Date: 10-Aug-2016
Date of Acceptance: 24-Jun-2016
URI: http://hdl.handle.net/10044/1/39065
DOI: http://dx.doi.org/10.1038/ncomms12354
ISSN: 2041-1723
Publisher: Nature Publishing Group
Journal / Book Title: Nature Communications
Volume: 7
Copyright Statement: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: MD Multidisciplinary
Publication Status: Published
Article Number: 12354
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons