Germline DNA Demethylation Dynamics and Imprint Erasure Through 5-Hydroxymethylcytosine

被引：556

作者：

Hackett, Jamie A. ^{[1
,2
]}

Sengupta, Roopsha ^{[1
,2
]}

Zylicz, Jan J. ^{[1
,2
,3
]}

Murakami, Kazuhiro ^{[1
,2
]}

Lee, Caroline ^{[1
,2
]}

Down, Thomas A. ^{[1
]}

Surani, M. Azim ^{[1
,2
,3
]}

机构：

[1] Univ Cambridge, Wellcome Trust Canc Res UK Gurdon Inst, Cambridge CB2 1QN, England

[2] Univ Cambridge, Wellcome Trust Med Res Council Stem Cell Inst, Cambridge CB2 1QN, England

[3] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 1QN, England

来源：

SCIENCE | 2013年 / 339卷 / 6118期

基金：

英国惠康基金;

关键词：

TET PROTEINS; MOUSE; METHYLATION; GENOME; CELL; 5-METHYLCYTOSINE; SPECIFICATION; MECHANISMS; CONVERSION; GENES;

D O I：

10.1126/science.1229277

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mouse primordial germ cells (PGCs) undergo sequential epigenetic changes and genome-wide DNA demethylation to reset the epigenome for totipotency. Here, we demonstrate that erasure of CpG methylation (5mC) in PGCs occurs via conversion to 5-hydroxymethylcytosine (5hmC), driven by high levels of TET1 and TET2. Global conversion to 5hmC initiates asynchronously among PGCs at embryonic day (E) 9.5 to E10.5 and accounts for the unique process of imprint erasure. Mechanistically, 5hmC enrichment is followed by its protracted decline thereafter at a rate consistent with replication-coupled dilution. The conversion to 5hmC is an important component of parallel redundant systems that drive comprehensive reprogramming in PGCs. Nonetheless, we identify rare regulatory elements that escape systematic DNA demethylation in PGCs, providing a potential mechanistic basis for transgenerational epigenetic inheritance.

引用

页码：448 / 452

页数：5

共 25 条

[1] Targets and dynamics of promoter DNA methylation during early mouse development [J].

Borgel, Julie ;

Guibert, Sylvain ;

Li, Yufeng ;

Chiba, Hatsune ;

Schuebeler, Dirk ;

Sasaki, Hiroyuki ;

Forne, Thierry ;

Weber, Michael .

NATURE GENETICS, 2010, 42 (12) :1093-U90

[2] Thymine DNA Glycosylase Is Essential for Active DNA Demethylation by Linked Deamination-Base Excision Repair [J].

Cortellino, Salvatore ;

Xu, Jinfei ;

Sannai, Mara ;

Moore, Robert ;

Caretti, Elena ;

Cigliano, Antonio ;

Le Coz, Madeleine ;

Devarajan, Karthik ;

Wessels, Andy ;

Soprano, Dianne ;

Abramowitz, Lara K. ;

Bartolomei, Marisa S. ;

Rambow, Florian ;

Bassi, Maria Rosaria ;

Bruno, Tiziana ;

Fanciulli, Maurizio ;

Renner, Catherine ;

Klein-Szanto, Andres J. ;

Matsumoto, Yoshihiro ;

Kobi, Dominique ;

Davidson, Irwin ;

Alberti, Christophe ;

Larue, Lionel ;

Bellacosa, Alfonso .

CELL, 2011, 146 (01) :67-79

[3] Tet1 Is Dispensable for Maintaining Pluripotency and Its Loss Is Compatible with Embryonic and Postnatal Development [J].

Dawlaty, Meelad M. ;

Ganz, Kibibi ;

Powell, Benjamin E. ;

Hu, Yueh-Chiang ;

Markoulaki, Styliani ;

Cheng, Albert W. ;

Gao, Qing ;

Kim, Jongpil ;

Choi, Sang-Woon ;

Page, David C. ;

Jaenisch, Rudolf .

CELL STEM CELL, 2011, 9 (02) :166-175

[4] Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation [J].

Ficz, Gabriella ;

Branco, Miguel R. ;

Seisenberger, Stefanie ;

Santos, Fatima ;

Krueger, Felix ;

Hore, Timothy A. ;

Marques, C. Joana ;

Andrews, Simon ;

Reik, Wolf .

NATURE, 2011, 473 (7347) :398-U589

[5] The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes [J].

Gu, Tian-Peng ;

Guo, Fan ;

Yang, Hui ;

Wu, Hai-Ping ;

Xu, Gui-Fang ;

Liu, Wei ;

Xie, Zhi-Guo ;

Shi, Linyu ;

He, Xinyi ;

Jin, Seung-gi ;

Iqbal, Khursheed ;

Shi, Yujiang Geno ;

Deng, Zixin ;

Szabo, Piroska E. ;

Pfeifer, Gerd P. ;

Li, Jinsong ;

Xu, Guo-Liang .

NATURE, 2011, 477 (7366) :606-U136

[6] Global profiling of DNA methylation erasure in mouse primordial germ cells [J].

Guibert, Sylvain ;

Forne, Thierry ;

Weber, Michael .

GENOME RESEARCH, 2012, 22 (04) :633-641

[7] Promoter DNA methylation couples genome-defence mechanisms to epigenetic reprogramming in the mouse germline [J].

Hackett, Jamie A. ;

Reddington, James P. ;

Nestor, Colm E. ;

Dunican, Donncha S. ;

Branco, Miguel R. ;

Reichmann, Judith ;

Reik, Wolf ;

Surani, M. Azim ;

Adams, Ian R. ;

Meehan, Richard R. .

DEVELOPMENT, 2012, 139 (19) :3623-3632

[8] Parallel mechanisms of epigenetic reprogramming in the germline [J].

Hackett, Jamie A. ;

Zylicz, Jan J. ;

Surani, M. Azim .

TRENDS IN GENETICS, 2012, 28 (04) :164-174

[9] Epigenetic reprogramming in mouse primordial germ cells [J].

Hajkova, P ;

Erhardt, S ;

Lane, N ;

Haaf, T ;

El-Maarri, O ;

Reik, W ;

Walter, J ;

Surani, MA .

MECHANISMS OF DEVELOPMENT, 2002, 117 (1-2) :15-23

[10] Chromatin dynamics during epigenetic reprogramming in the mouse germ line [J].

Hajkova, Petra ;

Ancelin, Katia ;

Waldmann, Tanja ;

Lacoste, Nicolas ;

Lange, Ulrike C. ;

Cesari, Francesca ;

Lee, Caroline ;

Almouzni, Genevieve ;

Schneider, Robert ;

Surani, M. Azim .

NATURE, 2008, 452 (7189) :877-U6

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