Postnatal DNA demethylation and its role in tissue maturation

被引：61

作者：

Reizel, Yitzhak ^{[1
,2
,3
]}

Sabag, Ofra ^{[1
]}

Skversky, Yael ^{[1
]}

Spiro, Adam ^{[1
]}

Steinberg, Benjamin ^{[1
]}

Bernstein, Diana ^{[2
,3
]}

Wang, Amber ^{[2
,3
]}

Kieckhaefer, Julia ^{[2
,3
]}

Li, Catherine ^{[4
]}

Pikarsky, Eli ^{[1
]}

Levin-Klein, Rena ^{[5
]}

Goren, Alon ^{[4
,6
]}

Rajewsky, Klaus ^{[7
]}

Kaestner, Klaus H. ^{[2
,3
]}

Cedar, Howard ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Sch Med, Dept Dev Biol & Canc Res, POB 12272, IL-91120 Jerusalem, Israel

[2] Univ Penn, Perelman Sch Med, Dept Genet, 12-126 Translat Res Ctr,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, 12-126 Translat Res Ctr,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA

[4] Broad Inst Harvard & MIT, BTL, Cambridge, MA 02142 USA

[5] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA

[6] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[7] Immune Regulat & Canc Max Delbruck Ctr, Mol Med MDC, Robert Rossle Str 10, D-13092 Berlin, Germany

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

美国国家卫生研究院; 欧洲研究理事会; 以色列科学基金会;

关键词：

EMBRYONIC STEM-CELLS; TET PROTEINS; EPIGENETIC MEMORY; HUMAN GENOME; METHYLATION; MOUSE; DIFFERENTIATION; TRANSCRIPTION; OXIDATION; CHROMATIN;

D O I：

10.1038/s41467-018-04456-6

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：

Development in mammals is accompanied by specific de novo and demethylation events that are thought to stabilize differentiated cell phenotypes. We demonstrate that a large percentage of the tissue-specific methylation pattern is generated postnatally. Demethylation in the liver is observed in thousands of enhancer-like sequences associated with genes that undergo activation during the first few weeks of life. Using. conditional gene ablation strategy we show that the removal of these methyl groups is stable and necessary for assuring proper hepatocyte gene expression and function through its effect on chromatin accessibility. These postnatal changes in methylation come about through exposure to hormone signaling. These results define the molecular rules of 5-methyl-cytosine regulation as an epigenetic mechanism underlying cellular responses to. changing environment.

引用

页数：11

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