#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues


The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied. To this end, we studied DNA methylation patterns in livers, hearts, and kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data were also available. Using the multi-species gene expression and methylation data for 7,723 genes, we were able to study the role of promoter DNA methylation in the evolution of gene regulation across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. However, we also found a large number of gene expression differences between species that might be explained, at least in part, by corresponding differences in methylation levels. In particular, we estimate that, in the tissues we studied, inter-species differences in promoter methylation might underlie as much as 12%–18% of differences in gene expression levels between humans and chimpanzees.


Vyšlo v časopise: A Genome-Wide Study of DNA Methylation Patterns and Gene Expression Levels in Multiple Human and Chimpanzee Tissues. PLoS Genet 7(2): e32767. doi:10.1371/journal.pgen.1001316
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001316

Souhrn

The modification of DNA by methylation is an important epigenetic mechanism that affects the spatial and temporal regulation of gene expression. Methylation patterns have been described in many contexts within and across a range of species. However, the extent to which changes in methylation might underlie inter-species differences in gene regulation, in particular between humans and other primates, has not yet been studied. To this end, we studied DNA methylation patterns in livers, hearts, and kidneys from multiple humans and chimpanzees, using tissue samples for which genome-wide gene expression data were also available. Using the multi-species gene expression and methylation data for 7,723 genes, we were able to study the role of promoter DNA methylation in the evolution of gene regulation across tissues and species. We found that inter-tissue methylation patterns are often conserved between humans and chimpanzees. However, we also found a large number of gene expression differences between species that might be explained, at least in part, by corresponding differences in methylation levels. In particular, we estimate that, in the tissues we studied, inter-species differences in promoter methylation might underlie as much as 12%–18% of differences in gene expression levels between humans and chimpanzees.


Zdroje

1. KingM-C

WilsonAC

1975 Evolution at Two Levels in Humans and Chimpanzees. Science 188 107 116

2. BrittenRJ

DavidsonEH

1969 Gene Regulation for Higher Cells: A Theory. Science 349 357

3. EnardW

KhaitovichP

KloseJ

ZöllnerS

HeissigF

2002 Intra- and interspecific variation in primate gene expression patterns. Science 296 340 343

4. KhaitovichP

MuetzelB

SheX

LachmannM

HellmannI

2004 Regional patterns of gene expression in human and chimpanzee brains. Genome Research 14 1462 1473

5. KhaitovichP

HellmannI

EnardW

NowickK

LeinweberM

2005 Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309 1850 1854

6. CáceresM

LachuerJ

ZapalaMA

RedmondJC

KudoL

2003 Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci USA 100 13030 13035

7. KaramanMW

HouckML

ChemnickLG

NagpalS

ChawannakulD

2003 Comparative analysis of gene-expression patterns in human and African great ape cultured fibroblasts. Genome Research 13 1619 1630

8. BlekhmanR

OshlackA

ChabotAE

SmythGK

GiladY

2008 Gene regulation in primates evolves under tissue-specific selection pressures. PLoS Genet 4 e1000271 doi:10.1371/journal.pgen.1000271

9. BlekhmanR

MarioniJC

ZumboP

StephensM

GiladY

2010 Sex-specific and lineage-specific alternative splicing in primates. Genome Research 20 180 189

10. PrabhakarS

ViselA

AkiyamaJA

ShoukryM

LewisKD

2008 Human-specific gain of function in a developmental enhancer. Science 321 1346 1350

11. BabbittCC

SilvermanJS

HaygoodR

ReiningaJM

RockmanMV

2010 Multiple Functional Variants in cis Modulate PDYN Expression. Molecular Biology and Evolution 27 465 479

12. WarnerLR

BabbittCC

PrimusAE

SeversonTF

HaygoodR

2009 Functional consequences of genetic variation in primates on tyrosine hydroxylase (TH) expression in vitro. Brain Research 1288 1 8

13. LoiselDA

RockmanMV

WrayGA

AltmannJ

AlbertsSC

2006 Ancient polymorphism and functional variation in the primate MHC-DQA1 5′ cis-regulatory region. Proc Natl Acad Sci USA 103 16331 16336

14. RockmanMV

HahnMW

SoranzoN

ZimprichF

GoldsteinDB

2005 Ancient and recent positive selection transformed opioid cis-regulation in humans. Plos Biol 3 e387 doi:10.1371/journal.pbio.0030387

15. PollardKS

SalamaSR

LambertN

LambotM-A

CoppensS

2006 An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443 167 172

16. BlekhmanR

OshlackA

GiladY

2009 Segmental Duplications Contribute to Gene Expression Differences Between Humans and Chimpanzees. Genetics 182 627 630

17. ChabotA

ShritRA

BlekhmanR

GiladY

2007 Using reporter gene assays to identify cis regulatory differences between humans and chimpanzees. Genetics 176 2069 2076

18. BabbittCC

FedrigoO

PfefferleAD

BoyleAP

HorvathJE

2010 Both Noncoding and Protein-Coding RNAs Contribute to Gene Expression Evolution in the Primate Brain. Genome Biology and Evolution 2 67 79

19. GorenA

SimchenG

FibachE

SzaboPE

TanimotoK

2006 Fine Tuning of Globin Gene Expression by DNA Methylation. PLoS ONE 1 e46 doi:10.1371/journal.pone.0000046

20. HeardE

DistecheCM

2006 Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes & Development 20 1848 1867

21. HeardE

ClercP

AvnerP

1997 X-Chromosome Inactivation in Mammals. Annu Rev Genet 31 571 610

22. SadoT

FennerMH

TanSS

TamP

ShiodaT

2000 X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation. Dev Biol 225 294 303

23. LiE

BeardC

JaenischR

1993 Role for DNA methylation in genomic imprinting. Nature 366 362 365

24. ReikW

2007 Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447 425 432

25. EggerG

LiangG

AparicioA

JonesPA

2004 Epigenetics in human disease and prospects for epigenetic therapy. Nature 429 457 463

26. IrizarryRA

Ladd-AcostaC

WenB

WuZ

MontanoC

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

27. 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

28. JaenischR

BirdA

2003 Epigenetic regulation of gene expression: how the genome intergrates intrinsic and environmental signals. Nature Genetics 33 245 254

29. LiE

BestorTH

JaenischR

1992 Targeted Mutation of the DNA Methyltransferase Gene Results in Embryonic Lethality. Cell 69 915 926

30. OkanoM

BellDW

HaberDA

LiE

1999 DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development. Cell 99 247 257

31. MurrellA

RakyanVK

BeckS

2005 From genome to epigenome. Hum Mol Genet 14 Spec No 1 R3 R10

32. SteinR

RazinA

CedarH

1982 In vitro methylation of the hamster adenine phosphoribosyltransferase gene inhibits its expression in mouse L cells. Proc Natl Acad Sci USA 79 3418 3422

33. HansenRS

GartlerSM

1990 5-Azacytidine-induced reactivation of the human X chromosome- linked PGK1 gene is associated with a large region of cytosine demethylation in the 5′ CpG island. Proc Natl Acad Sci USA 87 4174 4178

34. WeberM

HellmannI

StadlerMB

RamosL

PääboS

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

35. ThomsonJP

SkenePJ

SelfridgeJ

ClouaireT

GuyJ

2010 CpG islands influence chromatin structure via the CpG-binding protein Cfp1. Nature 464 1082 1086

36. WattF

MolloyPL

1988 Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes & Development 2 1136 1143

37. FengS

CokusSJ

ZhangX

ChenP-Y

BostickM

2010 Conservation and divergence of methylation patterning in plants and animals. Proceedings of the National Academy of Sciences 107 8689 8694

38. EnardW

FassbenderA

ModelF

AdorjanP

PaaboS

2004 Differences in DNA methylation patterns between humans and chimpanzees. Current Biology 14 R148 R149

39. Gama-SosaMA

MidgettRM

SlagelVA

GithensS

KuoKC

1983 Tissue-specific differences in DNA methylation in various mammals. Biochimica et Biophysica Acta 740 212 219

40. ZemachA

McDanielIE

SilvaP

ZilbermanD

2010 Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation. Science 1 7

41. IgarashiJ

MuroiS

KawashimaH

WangX

ShinojimaY

2009 Quantitative analysis of human tissue-specific differences in methylation. Biochemical and Biophysical Research Communications 376 658 664

42. RakyanVK

DownTA

ThorneNP

FlicekP

KuleshaE

2008 An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Research 18 1518 1529

43. EckhardtF

LewinJ

CorteseR

RakyanVK

AttwoodJ

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

44. KitamuraE

IgarashiJ

MorohashiA

HidaN

OinumaT

2007 Analysis of tissue-specific differentially methylated regions (TDMs) in humans. Genomics 89 326 337

45. GibbsJR

van der BrugMP

HernandezDG

TraynorBJ

NallsMA

2010 Abundant quantitative trait Loci exist for DNA methylation and gene expression in human brain. PLoS Genet 6 e1000952 doi:10.1371/journal.pgen.1000952

46. FarcasR

SchneiderE

FrauenknechtK

KondovaI

BontropR

2009 Differences in DNA methylation patterns and expression of the CCRK gene in human and nonhuman primate cortices. Mol Biol Evol 26 1379 1389

47. Gardiner-GardenM

FrommerM

1987 CpG Islands in Vertebrate Genomes. J Mol Biol 196 261 282

48. MaunakeaAK

NagarajanRP

BilenkyM

BallingerTJ

D'souzaC

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

49. RishiV

BhattacharyaP

ChatterjeeR

RozenbergJ

ZhaoJ

2010 CpG methylation of half-CRE sequences creates C/EBP{alpha} binding sites that activate some tissue-specific genes. Proc Natl Acad Sci USA 107 20311 20316

50. SunL

HuangL

NguyenP

BishtKS

Bar-SelaG

2008 DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res 68 2726 2735

51. GiusD

CuiH

BradburyCM

CookJ

SmartDK

2004 Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. Cancer Cell 6 361 371

52. BergerSL

KouzaridesT

ShiekhattarR

ShilatifardA

2009 An operational definition of epigenetics. Genes & Development 23 781 783

53. KentWJ

2002 BLAT--The BLAST-Like Alignment Tool. Genome Research 12 656 664

54. LiH

RuanJ

DurbinR

2008 Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Research 18 1851 1858

55. StoreyJD

TibshiraniR

2003 Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100 9440 9445

56. BackesC

KellerA

KuentzerJ

KneisslB

ComtesseN

2007 GeneTrail--advanced gene set enrichment analysis. Nucleic Acids Res 35 W186 192

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2011 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#