The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells

被引：738

作者：

Seisenberger, Stefanie ^{[1
]}

Andrews, Simon ^{[2
]}

Krueger, Felix ^{[2
]}

Arand, Julia ^{[3
]}

Walter, Joern ^{[3
]}

Santos, Fatima ^{[1
]}

Popp, Christian ^{[1
]}

Thienpont, Bernard ^{[1
,4
,5
]}

Dean, Wendy ^{[1
]}

Reik, Wolf ^{[1
,6
,7
]}

机构：

[1] Babraham Inst, Epigenet Programme, Cambridge CB22 3AT, England

[2] Babraham Inst, Bioinformat Grp, Cambridge CB22 3AT, England

[3] Univ Saarland, Dept Biol Sci, Inst Genet Epigenet, D-66123 Saarbrucken, Germany

[4] VIB, Vesalius Res Ctr, Lab Translat Genet, B-3000 Louvain, Belgium

[5] KULeuven, B-3000 Louvain, Belgium

[6] Univ Cambridge, Ctr Trophoblast Res, Cambridge CB2 3EG, England

[7] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England

来源：

MOLECULAR CELL | 2012年 / 48卷 / 06期

基金：

英国生物技术与生命科学研究理事会; 英国惠康基金;

关键词：

EPIGENETIC INHERITANCE; 5-HYDROXYMETHYLCYTOSINE; MECHANISMS; CHROMATIN; GENE; SPECIFICATION; TRANSCRIPTION; EXPRESSION; METHYLOME; LINEAGE;

D O I：

10.1016/j.molcel.2012.11.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Genome-wide DNA methylation reprogramming occurs in mouse primordial germ cells (PGCs) and preimplantation embryos, but the precise dynamics and biological outcomes are largely unknown. We have carried out whole-genome bisulfite sequencing (BS-Seq) and RNA-Seq across key stages from E6.5 epiblast to E16.5 PGCs. Global loss of methylation takes place during PGC expansion and migration with evidence for passive demethylation, but sequences that carry long-term epigenetic memory (imprints, CpG islands on the X chromosome, germline-specific genes) only become demethylated upon entry of PGCs into the gonads. The transcriptional profile of PGCs is tightly controlled despite global hypomethylation, with transient expression of the pluripotency network, suggesting that reprogramming and pluripotency are inextricably linked. Our results provide a framework for the understanding of the epigenetic ground state of pluripotency in the germline.

引用

页码：849 / 862

页数：14

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