X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs.

Stem Cell Reports
Authors
Keywords
Abstract

A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X chromosome. The loss of one of the two X chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X chromosome dosage dictates global DNA methylation levels in iPSCs.

Year of Publication
2018
Journal
Stem Cell Reports
Volume
10
Issue
5
Pages
1537-1550
Date Published
2018 05 08
ISSN
2213-6711
DOI
10.1016/j.stemcr.2018.03.019
PubMed ID
29681539
PubMed Central ID
PMC5995367
Links
Grant list
P01 GM099117 / GM / NIGMS NIH HHS / United States
P01 GM099134 / GM / NIGMS NIH HHS / United States
R01 GM115233 / GM / NIGMS NIH HHS / United States
T32 CA009056 / CA / NCI NIH HHS / United States