#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

DNA Methylation Landscapes of Human Fetal Development


Methylation of DNA is a key epigenetic mark. Adult tissues have highly distinct genome-wide DNA methylation signatures. How these signatures arise during human fetal development is largely unknown. Here, we studied DNA methylation profiles of four tissues (amnion, muscle, adrenal, pancreas) during first and second trimester of human fetal development. Already in the first trimester, a tissue-specific signature was found in each of the tissues. However, during the first and second trimester, a substantial number of genomic regions were found to gain and lose DNA methylation. Genomic regions that gained methylation were associated with the shut-down of developmental processes, while genomic regions that lose methylation were associated with the activation of tissue-specific functions. These findings on the DNA methylation landscape of human fetal development are important as they provide insight into regulatory elements that guide tissue specification and lead to organ functionality.


Vyšlo v časopise: DNA Methylation Landscapes of Human Fetal Development. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005583
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005583

Souhrn

Methylation of DNA is a key epigenetic mark. Adult tissues have highly distinct genome-wide DNA methylation signatures. How these signatures arise during human fetal development is largely unknown. Here, we studied DNA methylation profiles of four tissues (amnion, muscle, adrenal, pancreas) during first and second trimester of human fetal development. Already in the first trimester, a tissue-specific signature was found in each of the tissues. However, during the first and second trimester, a substantial number of genomic regions were found to gain and lose DNA methylation. Genomic regions that gained methylation were associated with the shut-down of developmental processes, while genomic regions that lose methylation were associated with the activation of tissue-specific functions. These findings on the DNA methylation landscape of human fetal development are important as they provide insight into regulatory elements that guide tissue specification and lead to organ functionality.


Zdroje

1. Byun HM, Siegmund KD, Pan F, Weisenberger DJ, Kanel G, Laird PW, et al. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet. 2009;18: 4808–4817. doi: 10.1093/hmg/ddp445 19776032

2. Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Gräf S, et al. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res. 2008;18: 1518–1529. doi: 10.1101/gr.077479.108 18577705

3. Ziller MJ, Gu H, Müller F, Donaghey J, Tsai LT- Y, Kohlbacher O, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2013;500: 477–81. doi: 10.1038/nature12433 23925113

4. Hon GC, Rajagopal N, Shen Y, McCleary DF, Yue F, Dang MD, et al. Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nat Genet. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2013;45: 1198–206. doi: 10.1038/ng.2746 23995138

5. Nagae G, Isagawa T, Shiraki N, Fujita T, Yamamoto S, Tsutsumi S, et al. Tissue-specific demethylation in CpG-poor promoters during cellular differentiation. Hum Mol Genet. 2011;20: 2710–2721. doi: 10.1093/hmg/ddr170 21505077

6. Slieker RC, Bos SD, Goeman JJ, Bovée JV, Talens RP, van der Breggen R, et al. Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k array. Epigenetics Chromatin. 2013;6: 26. doi: 10.1186/1756-8935-6-26 23919675

7. Gifford C a, Ziller MJ, Gu H, Trapnell C, Donaghey J, Tsankov A, et al. Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell. Elsevier Inc.; 2013;153: 1149–1163. doi: 10.1016/j.cell.2013.04.037 23664763

8. Maunakea AK, Nagarajan RP, Bilenky M, Ballinger TJ, D’Souza C, Fouse SD, et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature. Nature Publishing Group; 2010;466: 253–257. doi: 10.1038/nature09165 20613842

9. Smith ZD, Chan MM, Humm KC, Karnik R, Mekhoubad S, Regev A, et al. DNA methylation dynamics of the human preimplantation embryo. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2014;511: 611–615. doi: 10.1038/nature13581 25079558

10. Guo H, Zhu P, Yan L, Li R, Hu B, Lian Y, et al. The DNA methylation landscape of human early embryos. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2014;511: 606–10. doi: 10.1038/nature13544 25079557

11. Okae H, Chiba H, Hiura H, Hamada H, Sato A, Utsunomiya T, et al. Genome-wide analysis of DNA methylation dynamics during early human development. Oakey RJ, editor. PLoS Genet. 2014;10: e1004868. doi: 10.1371/journal.pgen.1004868 25501653

12. Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W. Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond B Biol Sci. 2013;368: 20110330. doi: 10.1098/rstb.2011.0330 23166394

13. Smith ZD, Chan MM, Mikkelsen TS, Gu H, Gnirke A, Regev A, et al. A unique regulatory phase of DNA methylation in the early mammalian embryo. Nature. Nature Publishing Group; 2012. pp. 339–344. doi: 10.1038/nature10960 22456710

14. Seisenberger S, Andrews S, Krueger F, Arand J, Walter J, Santos F, et al. The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells. Mol Cell. 2012;48: 849–862. doi: 10.1016/j.molcel.2012.11.001 23219530

15. Nazor KL, Altun G, Lynch C, Tran H, Harness J V., Slavin I, et al. Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives. Cell Stem Cell. 2012;10: 620–634. doi: 10.1016/j.stem.2012.02.013 22560082

16. Bocker MT, Hellwig I, Breiling A, Eckstein V, Ho AD, Lyko F. Genome-wide promoter DNA methylation dynamics of human hematopoietic progenitor cells during differentiation and aging. Blood. 2011;117: e182–9. doi: 10.1182/blood-2011-01-331926 21427290

17. Xie W, Schultz MD, Lister R, Hou Z, Rajagopal N, Ray P, et al. Epigenomic Analysis of Multilineage Differentiation of Human Embryonic Stem Cells. Cell. Elsevier Inc.; 2013;153: 1134–1148. doi: 10.1016/j.cell.2013.04.022 23664764

18. Brunner AL, Johnson DS, Kim SW, Valouev A, Reddy TE, Neff NF, et al. Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver. Genome Res. 2009;19: 1044–1056. doi: 10.1101/gr.088773.108 19273619

19. Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong CT, et al. Dynamic changes in the human methylome during differentiation. Genome Res. 2010;20: 320–331. doi: 10.1101/gr.101907.109 20133333

20. Bock C, Beerman I, Lien WH, Smith ZD, Gu H, Boyle P, et al. DNA Methylation Dynamics during In Vivo Differentiation of Blood and Skin Stem Cells. Mol Cell. 2012;47: 633–647. doi: 10.1016/j.molcel.2012.06.019 22841485

21. Gilsbach R, Preissl S, Grüning BA, Schnick T, Burger L, Benes V, et al. Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease. Nat Commun. Nature Publishing Group; 2014;5: 5288. doi: 10.1038/ncomms6288 25335909

22. Spiers H, Hannon E, Schalkwyk LC, Smith R, Wong CCY, O’Donovan MC, et al. Methylomic trajectories across human fetal brain development. Genome Res. 2015;25: 338–352. doi: 10.1101/gr.180273.114 25650246

23. Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, et al. High density DNA methylation array with single CpG site resolution. Genomics. Elsevier Inc.; 2011;98: 288–295. doi: 10.1016/j.ygeno.2011.07.007 21839163

24. Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, et al. An integrated encyclopedia of DNA elements in the human genome. Nature. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2012. pp. 57–74. doi: 10.1038/nature11247 22955616

25. Ernst J, Kheradpour P, Mikkelsen TS, Shoresh N, Ward LD, Epstein CB, et al. Mapping and analysis of chromatin state dynamics in nine human cell types. Nature. 2011;473: 43–49. doi: 10.1038/nature09906 21441907

26. Hou L, Zhao H. A review of post-GWAS prioritization approaches [Internet]. Frontiers in Genetics. 2013. p. 280. doi: 10.3389/fgene.2013.00280 24367376

27. Waterland RA, Michels KB. Epigenetic epidemiology of the developmental origins hypothesis. Annu Rev Nutr. Annual Reviews; 2007;27: 363–88. Available: http://www.annualreviews.org/doi/abs/10.1146/annurev.nutr.27.061406.093705 17465856

28. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008;105: 17046–17049. doi: 10.1073/pnas.0806560105 18955703

29. Sandoval J, Heyn HA, Moran S, Serra-Musach J, Pujana MA, Bibikova M, et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011;6: 692–702. 21593595

30. Bonder MJ, Kasela S, Kals M, Tamm R, Lokk K, Barragan I, et al. Genetic and epigenetic regulation of gene expression in fetal and adult human livers. BMC Genomics. 2014;15: 860. doi: 10.1186/1471-2164-15-860 25282492

31. Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.; 2012;13: 484–92. doi: 10.1038/nrg3230 22641018

32. Colaneri A, Wang T, Pagadala V, Kittur J, Staffa NG, Peddada SD, et al. A Minimal Set of Tissue-Specific Hypomethylated CpGs Constitute Epigenetic Signatures of Developmental Programming. Defossez P-A, editor. PLoS One. 2013;8: e72670. doi: 10.1371/journal.pone.0072670 24069155

33. Song F, Mahmood S, Ghosh S, Liang P, Smiraglia DJ, Nagase H, et al. Tissue specific differentially methylated regions (TDMR): Changes in DNA methylation during development. Genomics. 2009;93: 130–139. doi: 10.1016/j.ygeno.2008.09.003 18952162

34. Oliver-Krasinski JM, Stoffers D a. On the origin of the β cell. Genes and Development. 2008. pp. 1998–2021. doi: 10.1101/gad.1670808 18676806

35. Brink C. Promoter elements in endocrine pancreas development and hormone regulation. Cell Mol Life Sci. 2003;60: 1033–1048. 12861373

36. Leitges M, Neidhardt L, Haenig B, Herrmann BG, Kispert a. The paired homeobox gene Uncx4.1 specifies pedicles, transverse processes and proximal ribs of the vertebral column. Development. 2000;127: 2259–67. 10804169

37. Schulz R a, Yutzey KE. Calcineurin signaling and NFAT activation in cardiovascular and skeletal muscle development. Developmental Biology. 2004. pp. 1–16. 14729474

38. Pidsley R, Viana J, Hannon E, Spiers H, Troakes C, Al-Saraj S, et al. Methylomic profiling of human brain tissue supports a neurodevelopmental origin for schizophrenia. Genome Biol. 2014;15: 483. 25347937

39. Wiench M, John S, Baek S, Johnson TA, Sung M-H, Escobar T, et al. DNA methylation status predicts cell type-specific enhancer activity. EMBO J. 2011;30: 3028–3039. doi: 10.1038/emboj.2011.210 21701563

40. Roost MS, van Iperen L, Ariyurek Y, Buermans HP, Arindrarto W, Devalla HD, et al. KeyGenes, a Tool to Probe Tissue Differentiation Using a Human Fetal Transcriptional Atlas. Stem cell reports. 2015;4: 1112–24. doi: 10.1016/j.stemcr.2015.05.002 26028532

41. Stull JT, Kamm KE, Vandenboom R. Myosin light chain kinase and the role of myosin light chain phosphorylation in skeletal muscle. Archives of Biochemistry and Biophysics. 2011. pp. 120–128. doi: 10.1016/j.abb.2011.01.017 21284933

42. Bismuth K, Relaix F. Genetic regulation of skeletal muscle development. Experimental Cell Research. 2010. pp. 3081–3086. doi: 10.1016/j.yexcr.2010.08.018 20828559

43. Nelson SB, Schaffer AE, Sander M. The transcription factors Nkx6.1 and Nkx6.2 possess equivalent activities in promoting beta-cell fate specification in Pdx1+ pancreatic progenitor cells. Development. 2007;134: 2491–2500. 17537793

44. Heffer A, Pick L. Conservation and variation in Hox genes: how insect models pioneered the evo-devo field. Annu Rev Entomol. Annual Reviews; 2013;58: 161–79. doi: 10.1146/annurev-ento-120811-153601 23317041

45. Zhou VW, Goren A, Bernstein BE. Charting histone modifications and the functional organization of mammalian genomes. Nat Rev Genet. 2011;12: 7–18. doi: 10.1038/nrg2905 21116306

46. MacQuarrie KL, Yao Z, Fong AP, Diede SJ, Rudzinski ER, Hawkins DS, et al. Comparison of genome-wide binding of MyoD in normal human myogenic cells and rhabdomyosarcomas identifies regional and local suppression of promyogenic transcription factors. Mol Cell Biol. 2013;33: 773–84. doi: 10.1128/MCB.00916-12 23230269

47. Lokk K, Modhukur V, Rajashekar B. DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome …. 2014; Available: http://www.biomedcentral.com/content/pdf/gb-2014-15-4-r54.pdf

48. Calvanese V, Fernández AF, Urdinguio RG, Suárez-Alvarez B, Mangas C, Pérez-García V, et al. A promoter DNA demethylation landscape of human hematopoietic differentiation. Nucleic Acids Res. 2012;40: 116–131. doi: 10.1093/nar/gkr685 21911366

49. Rodriguez R. Regulation of the transcriptional program by DNA methylation during human αβ T-cell development. Nucleic acids …. 2014; Available: http://nar.oxfordjournals.org/content/early/2014/12/24/nar.gku1340.short

50. Kim M, Park YK, Kang TW, Lee SH, Rhee YH, Park JL, et al. Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo differentiation toward a neuronal lineage. Hum Mol Genet. 2014;23: 657–667. doi: 10.1093/hmg/ddt453 24087792

51. Miyata K, Miyata T, Nakabayashi K, Okamura K, Naito M, Kawai T, et al. DNA methylation analysis of human myoblasts during in vitro myogenic differentiation: de novo methylation of promoters of muscle-related genes and its involvement in transcriptional down-regulation. Hum Mol Genet. 2015;24: 410–23. doi: 10.1093/hmg/ddu457 25190712

52. Zhou Y, Hu Z. Genome-Wide Demethylation by 5-aza-2’-Deoxycytidine Alters the Cell Fate of Stem/Progenitor Cells. Stem Cell Reviews and Reports. 2014.

53. Hupkes M, Jonsson MKB, Scheenen WJ, van Rotterdam W, Sotoca AM, van Someren EP, et al. Epigenetics: DNA demethylation promotes skeletal myotube maturation [Internet]. The FASEB Journal. 2011. pp. 3861–3872. doi: 10.1096/fj.11-186122 21795504

54. Smallwood SA, Lee HJ, Angermueller C, Krueger F, Saadeh H, Peat J, et al. Single-cell genome-wide bisulfite sequencing for assessing epigenetic heterogeneity. Nat Methods. 2014;11: 817–20. doi: 10.1038/nmeth.3035 25042786

55. Shapiro E, Biezuner T, Linnarsson S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat Rev Genet. 2013;14: 618–30. doi: 10.1038/nrg3542 23897237

56. Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345: 1247125. doi: 10.1126/science.1247125 25035496

57. Mill J, Heijmans BT. From promises to practical strategies in epigenetic epidemiology. Nat Rev Genet. 2013;14: 585–94. doi: 10.1038/nrg3405 23817309

58. Roost MS, van Iperen L, de Melo Bernardo A, Mummery CL, Carlotti F, de Koning EJ, et al. Lymphangiogenesis and angiogenesis during human fetal pancreas development. Vasc Cell. BioMed Central Ltd; 2014;6: 22. doi: 10.1186/2045-824X-6-22 25785186

59. Hansen KD, Aryee M. minfi: Analyze Illumina’s 450k methylation arrays. R package version 1.6.0. Bioconductor; 2013.

60. Chen Y, Lemire M, Choufani S, Butcher DT, Grafodatskaya D, Zanke BW, et al. Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics. 2013;8: 203–9. doi: 10.4161/epi.23470 23314698

61. Du P, Kibbe WA, Lin SM. lumi: a pipeline for processing Illumina microarray. Bioinformatics. 2008;24: 1547–8. doi: 10.1093/bioinformatics/btn224 18467348

62. Teschendorff AE, Marabita F, Lechner M, Bartlett T, Tegner J, Gomez-Cabrero D, et al. A beta-mixture quantile normalization method for correcting probe design bias in Illumina Infinium 450 k DNA methylation data. Bioinformatics. 2013;29: 189–96. doi: 10.1093/bioinformatics/bts680 23175756

63. Feber A, Guilhamon P, Lechner M, Fenton T, Wilson GA, Thirlwell C, et al. Using high-density DNA methylation arrays to profile copy number alterations. Genome Biol. 2014;15: R30. doi: 10.1186/gb-2014-15-2-r30 24490765

64. Morris TJ, Butcher LM, Feber A, Teschendorff AE, Chakravarthy AR, Wojdacz TK, et al. ChAMP: 450k Chip Analysis Methylation Pipeline. Bioinformatics. 2014;30: 428–430. doi: 10.1093/bioinformatics/btt684 24336642

65. Koenker R. quantreg: Quantile Regression [Internet]. 2013. Available: http://cran.r-project.org/package=quantreg

66. Wickham H. ggplot2: elegant graphics for data analysis. Springer, New York. Springer, New York; 2009.

67. Durinck S, Bullard J. GenomeGraphs: Plotting genomic information from Ensembl. R package version 1.22.0.

68. Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. Nature Publishing Group; 2009;4: 44–57. doi: 10.1038/nprot.2008.211 19131956

69. Robinson MD, McCarthy DJ, Smyth GK. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2009;26: 139–140. doi: 10.1093/bioinformatics/btp616 19910308

70. Robinson MD, Smyth GK. Small-sample estimation of negative binomial dispersion, with applications to SAGE data. Biostatistics. 2008;9: 321–32. Available: http://biostatistics.oxfordjournals.org/content/9/2/321.short 17728317

71. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: Archive for functional genomics data sets—Update. Nucleic Acids Res. 2013;41: D991–5. doi: 10.1093/nar/gks1193 23193258

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 10
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

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#