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

被引：32

作者：

Pasque, Vincent ^{[1
,3
]}

Karnik, Rahul ^{[2
]}

Chronis, Constantinos ^{[1
]}

Petrella, Paula ^{[1
]}

Langerman, Justin ^{[1
]}

Bonora, Giancarlo ^{[1
]}

Song, Juan ^{[3
]}

Vanheer, Lotte ^{[3
]}

Dimashkie, Anupama Sadhu ^{[1
]}

Meissner, Alexander ^{[2
,4
]}

Plath, Kathrin ^{[1
]}

机构：

[1] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Jonsson Comprehens Canc Ctr, David Geffen Sch Med,Dept Biol Chem,Mol B, 615 Charles E Young Dr South,BSRB 390D, Los Angeles, CA 90095 USA

[2] Harvard Univ, Broad Inst MIT & Harvard, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[3] Univ Leuven, KU Leuven, Leuven Canc Inst, Dept Dev & Regenerat,Leuven Stem Cell Inst, Herestr 49, B-3000 Leuven, Belgium

[4] Max Planck Inst Mol Genet, Dept Genome Regulat, Ihnestr 63-73, D-14195 Berlin, Germany

来源：

STEM CELL REPORTS | 2018年 / 10卷 / 05期

基金：

比利时弗兰德研究基金会;

关键词：

PLURIPOTENT; GENOME; CELLS; STATE; GENE; HYPOMETHYLATION; DEMETHYLATION; EXPRESSION; CHROMATIN;

D O I：

10.1016/j.stemcr.2018.03.019

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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.

引用

页码：1537 / 1550

页数：14

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