Early-life nutrition modulates the epigenetic state of specific rDNA genetic variants in mice

被引：82

作者：

Holland, Michelle L. ^{[1
]}

Lowe, Robert ^{[1
]}

Caton, Paul W. ^{[2
]}

Gemma, Carolina ^{[1
,5
]}

Carbajosa, Guillermo ^{[1
,6
]}

Danson, Amy F. ^{[1
]}

Carpenter, Asha A. M. ^{[3
,4
]}

Loche, Elena ^{[3
,4
]}

Ozanne, Susan E. ^{[3
,4
]}

Rakyan, Vardhman K. ^{[1
]}

机构：

[1] Queen Mary Univ London, Blizard Inst, Barts & London Sch Med & Dent, London E1 2AT, England

[2] Kings Coll London, Div Diabet & Nutr Sci, 150 Stamford St, London SE1 9NH, England

[3] Univ Cambridge, Metab Res Labs, Cambridge CB2 0QQ, England

[4] Addenbrookes Hosp, MRC Metab Dis Unit, Inst Metab Sci, Cambridge CB2 0QQ, England

[5] Imperial Coll London, Dept Surg & Canc, Hammersmith Hosp Campus, London, England

[6] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England

来源：

SCIENCE | 2016年 / 353卷 / 6298期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会; 英国工程与自然科学研究理事会; 欧盟第七框架计划;

关键词：

RIBOSOMAL-RNA GENES; DIET;

D O I：

10.1126/science.aaf7040

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：

A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.

引用

页码：495 / 498

页数：4

共 19 条

[1] Decreased ovarian reserve, dysregulation of mitochondrial biogenesis, and increased lipid peroxidation in female mouse offspring exposed to an obesogenic maternal diet [J].

Aiken, Catherine E. ;

Tarry-Adkins, Jane L. ;

Penfold, Naomi C. ;

Dearden, Laura ;

Ozanne, Susan E. .

FASEB JOURNAL, 2016, 30 (04) :1548-1556

[2] Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila [J].

Aldrich, John C. ;

Maggert, Keith A. .

PLOS GENETICS, 2015, 11 (04)

[3] Maternal Nutrition Induces Pervasive Gene Expression Changes but No Detectable DNA Methylation Differences in the Liver of Adult Offspring [J].

Cannon, Matthew V. ;

Buchner, David A. ;

Hester, James ;

Miller, Hadley ;

Sehayek, Ephraim ;

Nadeau, Joseph H. ;

Serre, David .

PLOS ONE, 2014, 9 (03)

[4]

DEV VG, 1977, GENETICS, V86, P389

[5] Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment [J].

El Hajj, Nady ;

Schneider, Eberhard ;

Lehnen, Harald ;

Haaf, Thomas .

REPRODUCTION, 2014, 148 (06) :R111-R120

[6] Intergenerational epigenetic inheritance in models of developmental programming of adult disease [J].

Fernandez-Twinn, Denise S. ;

Constancia, Miguel ;

Ozanne, Susan E. .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2015, 43 :85-95

[7] EARLY DEVELOPMENTAL CONDITIONING OF LATER HEALTH AND DISEASE: PHYSIOLOGY OR PATHOPHYSIOLOGY? [J].

Hanson, M. A. ;

Gluckman, P. D. .

PHYSIOLOGICAL REVIEWS, 2014, 94 (04) :1027-1076

[8] Regulation of ribosomal DNA amplification by the TOR pathway [J].

Jack, Carmen V. ;

Cruz, Cristina ;

Hull, Ryan M. ;

Keller, Markus A. ;

Ralser, Markus ;

Houseley, Jonathan .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (31) :9674-9679

[9] PRIMARY PROCESSING OF MAMMALIAN RIBOSOMAL-RNA INVOLVES 2 ADJACENT CLEAVAGES AND IS NOT SPECIES-SPECIFIC [J].

KASS, S ;

CRAIG, N ;

SOLLNERWEBB, B .

MOLECULAR AND CELLULAR BIOLOGY, 1987, 7 (08) :2891-2898

[10] Intergenic transcripts regulate the epigenetic state of rRNA genes [J].

Mayer, Christine ;

Schmitz, Kerstin-Maike ;

Li, Junwei ;

Grummt, Ingrid ;

Santoro, Raffaella .

MOLECULAR CELL, 2006, 22 (03) :351-361

← 1 2 →