Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles

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Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease.

Vyšlo v časopise: Season of Conception in Rural Gambia Affects DNA Methylation at Putative Human Metastable Epialleles. PLoS Genet 6(12): e32767. doi:10.1371/journal.pgen.1001252
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001252

Souhrn

Zdroje

1. JaenischR

BirdA

2003 Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33 Suppl 245 254

2. IrizarryRA

Ladd-AcostaC

WenB

WuZ

MontanoC

2009 The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 41 178 186

3. MaunakeaAK

NagarajanRP

BilenkyM

BallingerTJ

D'SouzaC

2010 Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466 253 257

4. GluckmanPD

HansonMA

BuklijasT

LowFM

BeedleAS

2009 Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol 5 401 408

5. WaterlandRA

MichelsKB

2007 Epigenetic Epidemiology of the Developmental Origins Hypothesis. Annu Rev Nutr 27 363 388

6. RichardsEJ

2006 Inherited epigenetic variation—revisiting soft inheritance. Nat Rev Genet 7 395 401

7. MorganHD

SutherlandHG

MartinDI

WhitelawE

1999 Epigenetic inheritance at the agouti locus in the mouse [see comments]. NatGenet 23 314 318

8. VasicekTJ

ZengL

GuanXJ

ZhangT

CostantiniF

1997 Two dominant mutations in the mouse fused gene are the result of transposon insertions. Genetics 147 777 786

9. WolffGL

RobertsDW

MountjoyKG

1999 Physiological consequences of ectopic agouti gene expression: the yellow obese mouse syndrome. Physiol Genomics 1 151 163

10. DolinoyDC

HuangD

JirtleRL

2007 Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci U S A 104 13056 13061

11. WaterlandRA

DolinoyDC

LinJR

SmithCA

ShiX

2006 Maternal methyl supplements increase offspring DNA methylation at Axin fused. Genesis 44 401 406

12. WaterlandRA

JirtleRL

2003 Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23 5293 5300

13. WaterlandRA

GarzaC

1999 Potential mechanisms of metabolic imprinting that lead to chronic disease. AmJClinNutr 69 179 197

14. CedarH

BergmanY

2009 Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10 295 304

15. ShenL

KondoY

GuoY

ZhangJ

ZhangL

2007 Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet 3 e181 doi:10.1371/journal.pgen.0030181

16. KatariS

TuranN

BibikovaM

ErinleO

ChalianR

2009 DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet 18 3769 3778

17. AmbrosiniA

PaulS

HuS

RiethmanH

2007 Human subtelomeric duplicon structure and organization. Genome Biol 8 R151

18. HeijmansBT

TobiEW

SteinAD

PutterH

BlauwGJ

2008 Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A 105 17046 17049

19. TobiEW

LumeyLH

TalensRP

KremerD

PutterH

2009 DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18 4046 4053

20. DrukerR

BruxnerTJ

LehrbachNJ

WhitelawE

2004 Complex patterns of transcription at the insertion site of a retrotransposon in the mouse. Nucleic Acids Res 32 5800 5808

21. RakyanVK

BlewittME

DrukerR

PreisJI

WhitelawE

2002 Metastable epialleles in mammals. Trends Genet 18 348 351

22. KerkelK

SpadolaA

YuanE

KosekJ

JiangL

2008 Genomic surveys by methylation-sensitive SNP analysis identify sequence-dependent allele-specific DNA methylation. Nat Genet 40 904 908

23. LigtenbergMJ

KuiperRP

ChanTL

GoossensM

HebedaKM

2009 Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1. Nat Genet 41 112 117

24. ReikW

WalterJ

2001 Genomic imprinting: parental influence on the genome. Nat Rev Genet 2 21 32

25. LingJQ

LiT

HuJF

VuTH

ChenHL

2006 CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science 312 269 272

26. PrenticeAM

ColeTJ

FoordFA

LambWH

WhiteheadRG

1987 Increased birthweight after prenatal dietary supplementation of rural African women. Am J Clin Nutr 46 912 925

27. Rayco-SolonP

FulfordAJ

PrenticeAM

2005 Differential effects of seasonality on preterm birth and intrauterine growth restriction in rural Africans. Am J Clin Nutr 81 134 139

28. MooreSE

ColeTJ

PoskittEM

SonkoBJ

WhiteheadRG

1997 Season of birth predicts mortality in rural Gambia. Nature 388 434

29. YangAS

EstecioMR

DoshiK

KondoY

TajaraEH

2004 A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements. Nucleic Acids Res 32 e38

30. RakyanVK

ChongS

ChampME

CuthbertPC

MorganHD

2003 Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci U S A 100 2538 2543

31. WolffGL

1965 Body Composition and Coat Color Correlation in Different Phenotypes of “Viable Yellow” Mice. Science 147 1145 1147

32. FeinbergAP

IrizarryRA

2010 Evolution in health and medicine Sackler colloquium: Stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proc Natl Acad Sci U S A 107 Suppl 1 1757 1764

33. FragaMF

BallestarE

PazMF

RoperoS

SetienF

2005 Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci U S A 102 10604 10609

34. KaminskyZA

TangT

WangSC

PtakC

OhGH

2009 DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41 240 245

35. MacchiaPE

LapiP

KrudeH

PirroMT

MisseroC

1998 PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet 19 83 86

36. AbelsonJF

KwanKY

O'RoakBJ

BaekDY

StillmanAA

2005 Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310 317 320

37. JirtleRL

SkinnerMK

2007 Environmental epigenomics and disease susceptibility. Nat Rev Genet 8 253 262

38. WaterlandRA

LinJR

SmithCA

JirtleRL

2006 Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15 705 716

39. WeaverIC

CervoniN

ChampagneFA

D'AlessioAC

SharmaS

2004 Epigenetic programming by maternal behavior. Nat Neurosci 7 847 854

40. KaatiG

BygrenLO

EdvinssonS

2002 Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period. Eur J Hum Genet 10 682 688

41. PembreyME

BygrenLO

KaatiG

EdvinssonS

NorthstoneK

2006 Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14 159 166

42. BatesCJ

FullerNJ

PrenticeAM

1986 Folate status during pregnancy and lactation in a West African rural community. Hum Nutr Clin Nutr 40 3 13

43. RusieckiJA

BaccarelliA

BollatiV

TarantiniL

MooreLE

2008 Global DNA hypomethylation is associated with high serum-persistent organic pollutants in Greenlandic Inuit. Environ Health Perspect 116 1547 1552

44. ZhangYJ

RossnerPJr

ChenY

AgrawalM

WangQ

2006 Aflatoxin B1 and polycyclic aromatic hydrocarbon adducts, p53 mutations and p16 methylation in liver tissue and plasma of hepatocellular carcinoma patients. Int J Cancer 119 985 991

45. LeonardWR

1989 Protection of children from seasonal nutritional stress in an Andean agricultural community. Eur J Clin Nutr 43 597 602

46. RaoS

KanadeAN

YajnikCS

FallCH

2009 Seasonality in maternal intake and activity influence offspring's birth size among rural Indian mothers—Pune Maternal Nutrition Study. Int J Epidemiol 38 1094 1103

47. StraussWM

2001 Preparation of genomic DNA from mammalian tissue.

AusubelFM

Current protocols in molecular biology New York J. Wiley & Sons 2.2.1 2.2.3

48. PetryCJ

Rayco-SolonP

FulfordAJ

SteadJD

WingateDL

2009 Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth. Hum Genet 126 375 384

49. MillerSA

DykesDD