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
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2010 Číslo 5
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