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

Vincent Pasque, Rahul Karnik, Constantinos Chronis, Paula Petrella, Justin Langerman, Giancarlo Bonora, Juan Song, Lotte Vanheer, Anupama Sadhu Dimashkie, Alexander Meissner, Kathrin Plath
2018 Stem Cell Reports  
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
more » ... ites 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.
doi:10.1016/j.stemcr.2018.03.019 pmid:29681539 pmcid:PMC5995367 fatcat:wunlgctwxfcxtggnfwapajj6j4