Ordered chromatin changes and human X chromosome reactivation by cell fusion-mediated pluripotent reprogramming
File(s)
Published version
Author(s)
Fisher, AG
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.
Date Issued
2016-08-10
Date Acceptance
2016-06-24
Citation
Nature Communications, 2016, 7 (7)
ISSN
2041-1723
Publisher
Nature Publishing Group: Nature Communications
Journal / Book Title
Nature Communications
Volume
7
Issue
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/
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/
License URL
Sponsor
Commission of the European Communities
Grant Number
294627
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
EMBRYONIC STEM-CELLS
XIST RNA
INACTIVE-X
DNA METHYLATION
GENE-EXPRESSION
SOMATIC-CELLS
HYBRID-CELLS
LOCALIZATION
MAINTENANCE
HISTONE
Animals
Cell Fusion
Cell Line
Cell Nucleus
Cellular Reprogramming
Chromatin
Chromosomes, Human, X
Epigenesis, Genetic
Female
Fibroblasts
Histones
Humans
Induced Pluripotent Stem Cells
Male
Mice
Mitosis
Mouse Embryonic Stem Cells
RNA, Long Noncoding
X Chromosome Inactivation
Cell Line
Chromosomes, Human, X
Cell Nucleus
Chromatin
Fibroblasts
Animals
Humans
Mice
Histones
Cell Fusion
Mitosis
Epigenesis, Genetic
Female
Male
X Chromosome Inactivation
Induced Pluripotent Stem Cells
RNA, Long Noncoding
Cellular Reprogramming
Mouse Embryonic Stem Cells
Publication Status
Published
Article Number
ARTN 12354