DNA methylation signatures link prenatal famine exposure to growth and metabolism

被引：399

作者：

Tobi, Elmar W. ^{[1
]}

Goeman, Jelle J. ^{[1
]}

Monajemi, Ramin ^{[1
]}

Gu, Hongcang ^{[2
]}

Putter, Hein ^{[1
]}

Zhang, Yanju ^{[1
]}

Slieker, Roderick C. ^{[1
]}

Stok, Arthur P. ^{[1
]}

Thijssen, Peter E. ^{[1
]}

Mueller, Fabian ^{[3
]}

van Zwet, Erik W. ^{[1
]}

Bock, Christoph ^{[3
,4
,5
]}

Meissner, Alexander ^{[2
,6
]}

Lumey, L. H. ^{[1
,7
]}

Slagboom, P. Eline ^{[1
]}

Heijmans, Bastiaan T. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, NL-2300 RC Leiden, Netherlands

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

[3] Max Planck Inst Informat, D-66123 Saarbrucken, Germany

[4] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria

[5] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria

[6] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[7] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院;

关键词：

DEVELOPMENTAL ORIGINS; GENE-EXPRESSION; CPG METHYLATION; CPT1A LOCUS; OBESITY; CELLS; AGE; UNDERNUTRITION; ASSOCIATION; PREDICTION;

D O I：

10.1038/ncomms6592

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：

Periconceptional diet may persistently influence DNA methylation levels with phenotypic consequences. However, a comprehensive assessment of the characteristics of prenatal malnutrition-associated differentially methylated regions (P-DMRs) is lacking in humans. Here we report on a genome-scale analysis of differential DNA methylation in whole blood after periconceptional exposure to famine during the Dutch Hunger Winter. We show that P-DMRs preferentially occur at regulatory regions, are characterized by intermediate levels of DNA methylation and map to genes enriched for differential expression during early development. Validation and further exploratory analysis of six P-DMRs highlight the critical role of gestational timing. Interestingly, differential methylation of the P-DMRs extends along pathways related to growth and metabolism. P-DMRs located in INSR and CPT1A have enhancer activity in vitro and differential methylation is associated with birth weight and serum LDL cholesterol. Epigenetic modulation of pathways by prenatal malnutrition may promote an adverse metabolic phenotype in later life.

引用

页数：13

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