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Aging and Chronic Sun Exposure Cause Distinct Epigenetic Changes in Human Skin


Epigenetic changes are widely considered to play an important role in aging, but experimental evidence to support this hypothesis has been scarce. We have used array-based analysis to determine genome-scale DNA methylation patterns from human skin samples and to investigate the effects of aging, chronic sun exposure, and tissue variation. Our results reveal a high degree of tissue specificity in the methylation patterns and also showed very little interindividual variation within tissues. Data stratification by age revealed that DNA from older individuals was characterized by a specific hypermethylation pattern affecting less than 1% of the markers analyzed. Interestingly, stratification by sun exposure produced a fundamentally different pattern with a significant trend towards hypomethylation. Our results thus identify defined age-related DNA methylation changes and suggest that these alterations might contribute to the phenotypic changes associated with skin aging.


Vyšlo v časopise: Aging and Chronic Sun Exposure Cause Distinct Epigenetic Changes in Human Skin. PLoS Genet 6(5): e32767. doi:10.1371/journal.pgen.1000971
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000971

Souhrn

Epigenetic changes are widely considered to play an important role in aging, but experimental evidence to support this hypothesis has been scarce. We have used array-based analysis to determine genome-scale DNA methylation patterns from human skin samples and to investigate the effects of aging, chronic sun exposure, and tissue variation. Our results reveal a high degree of tissue specificity in the methylation patterns and also showed very little interindividual variation within tissues. Data stratification by age revealed that DNA from older individuals was characterized by a specific hypermethylation pattern affecting less than 1% of the markers analyzed. Interestingly, stratification by sun exposure produced a fundamentally different pattern with a significant trend towards hypomethylation. Our results thus identify defined age-related DNA methylation changes and suggest that these alterations might contribute to the phenotypic changes associated with skin aging.


Zdroje

1. FragaMF

EstellerM

2007 Epigenetics and aging: the targets and the marks. Trends Genet 23 413 418

2. BirdA

2007 Perceptions of epigenetics. Nature 447 396 398

3. SuzukiMM

BirdA

2008 DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9 465 476

4. KouzaridesT

2007 Chromatin modifications and their function. Cell 128 693 705

5. EstellerM

2002 CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene 21 5427 5440

6. JaenischR

BirdA

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

7. FeinbergAP

2007 Phenotypic plasticity and the epigenetics of human disease. Nature 447 433 440

8. 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

9. BjornssonHT

SigurdssonMI

FallinMD

IrizarryRA

AspelundT

2008 Intra-individual change over time in DNA methylation with familial clustering. Jama 299 2877 2883

10. MartinGM

2005 Epigenetic drift in aging identical twins. Proc Natl Acad Sci U S A 102 10413 10414

11. EckhardtF

LewinJ

CorteseR

RakyanVK

AttwoodJ

2006 DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 38 1378 1385

12. GilharA

UllmannY

KarryR

ShalaginovR

AssyB

2004 Ageing of human epidermis: the role of apoptosis, Fas and telomerase. Br J Dermatol 150 56 63

13. BaumannL

2007 Skin ageing and its treatment. J Pathol 211 241 251

14. BibikovaM

LeJ

BarnesB

Saedinia-MelnykS

ZhouL

2009 Genome-wide DNA methylation profiling using Infinium assay. Epigenomics 1 177 200

15. WarneckePM

StirzakerC

MelkiJR

MillarDS

PaulCL

1997 Detection and measurement of PCR bias in quantitative methylation analysis of bisulphite-treated DNA. Nucleic Acids Res 25 4422 4426

16. WeberM

HellmannI

StadlerMB

RamosL

PaaboS

2007 Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 39 457 466

17. IllingworthR

KerrA

DesousaD

JorgensenH

EllisP

2008 A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biol 6 e22 doi:10.1371/journal.pbio.0060022

18. BallMP

LiJB

GaoY

LeeJH

LeProustEM

2009 Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells. Nat Biotechnol 27 361 368

19. HeardE

ClercP

AvnerP

1997 X-chromosome inactivation in mammals. Annu Rev Genet 31 571 610

20. TobinDJ

2006 Biochemistry of human skin–our brain on the outside. Chem Soc Rev 35 52 67

21. MollR

DivoM

LangbeinL

2008 The human keratins: biology and pathology. Histochem Cell Biol 129 705 733

22. ProkschE

BrandnerJM

JensenJM

2008 The skin: an indispensable barrier. Exp Dermatol 17 1063 1072

23. ByrneC

TainskyM

FuchsE

1994 Programming gene expression in developing epidermis. Development 120 2369 2383

24. TroyTC

TurksenK

2005 Commitment of embryonic stem cells to an epidermal cell fate and differentiation in vitro. Dev Dyn 232 293 300

25. IkehataH

KawaiK

KomuraJ

SakatsumeK

WangL

2008 UVA1 genotoxicity is mediated not by oxidative damage but by cyclobutane pyrimidine dimers in normal mouse skin. J Invest Dermatol 128 2289 2296

26. WinterH

LangbeinL

PraetzelS

JacobsM

RogersMA

1998 A novel human type II cytokeratin, K6hf, specifically expressed in the companion layer of the hair follicle. J Invest Dermatol 111 955 962

27. ChenJ

JaegerK

DenZ

KochPJ

SundbergJP

2008 Mice expressing a mutant Krt75 (K6hf) allele develop hair and nail defects resembling pachyonychia congenita. J Invest Dermatol 128 270 279

28. TownleyAK

FengY

SchmidtK

CarterDA

PorterR

2008 Efficient coupling of Sec23-Sec24 to Sec13-Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development. J Cell Sci 121 3025 3034

29. TomikawaJ

FukatsuK

TanakaS

ShiotaK

2006 DNA methylation-dependent epigenetic regulation of dimethylarginine dimethylaminohydrolase 2 gene in trophoblast cell lineage. J Biol Chem 281 12163 12169

30. BackdahlL

HerberthM

WilsonG

TateP

CamposLS

2009 Gene body methylation of the dimethylarginine dimethylamino-hydrolase 2 (Ddah2) gene is an epigenetic biomarker for neural stem cell differentiation. Epigenetics 4 248 254

31. LangemeijerSM

KuiperRP

BerendsM

KnopsR

AslanyanMG

2009 Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 41 838 842

32. WilsonVL

JonesPA

1983 DNA methylation decreases in aging but not in immortal cells. Science 220 1055 1057

33. ChristensenBC

HousemanEA

MarsitCJ

ZhengS

WrenschMR

2009 Aging and environmental exposures alter tissue-specific DNA methylation dependent upon CpG island context. PLoS Genet 5 e1000602 doi:10.1371/journal.pgen.1000602

34. RakyanVK

DownTA

MaslauS

AndrewT

YangTP

2010 Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domains. Genome Res 20 434 439

35. TeschendorffAE

MenonU

Gentry-MaharajA

RamusSJ

WeisenbergerDJ

2010 Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer. Genome Res 20 440 446

36. AhujaN

LiQ

MohanAL

BaylinSB

IssaJP

1998 Aging and DNA methylation in colorectal mucosa and cancer. Cancer Res 58 5489 5494

37. MaegawaS

HinkalG

KimHS

ShenL

ZhangL

2010 Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res 20 332 340

38. ErshlerWB

LongoDL

1997 Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst 89 1489 1497

39. Bruch-GerharzD

RuzickaT

Kolb-BachofenV

1998 Nitric oxide in human skin: current status and future prospects. J Invest Dermatol 110 1 7

40. SudelKM

VenzkeK

Knussmann-HartigE

MollI

StabF

2003 Tight control of matrix metalloproteinase-1 activity in human skin. Photochem Photobiol 78 355 360

41. BolstadB

2001 Probe Level Quantile Normalization of High Density Oligonucleotide Array Data. Berkeley University of California

42. BenjaminiY

HochbergY

1995 Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society B 57 289 300

43. BolstadBM

IrizarryRA

AstrandM

SpeedTP

2003 A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19 185 193

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Genetika Reprodukčná medicína

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PLOS Genetics


2010 Číslo 5
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