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The tissue-specific aspect of genome-wide DNA methylation in newborn and placental tissues: implications for epigenetic epidemiologic studies

Published online by Cambridge University Press:  24 April 2020

Emilie M. Herzog ,
Alex J. Eggink ,
Sten P. Willemsen ,
Roderick C. Slieker ,
Janine F. Felix ,
Andrew P. Stubbs ,
Peter J. van der Spek ,
Joyce B. J. van Meurs ,
Bastiaan T. Heijmans  and
Régine P. M. Steegers-Theunissen Open the ORCID record for Régine P. M. Steegers-Theunissen [Opens in a new window]
Emilie M. Herzog
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Alex J. Eggink
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Sten P. Willemsen
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Biostatistics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Roderick C. Slieker
Affiliation:
Department of Molecular Epidemiology, Leiden University Medical Centre, Postbus 9600, 2300 RCLeiden, The Netherlands
Janine F. Felix
Affiliation:
Department of Epidemiology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Generation R Study Group, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Paediatrics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Andrew P. Stubbs
Affiliation:
Department of Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Peter J. van der Spek
Affiliation:
Department of Bioinformatics, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Joyce B. J. van Meurs
Affiliation:
Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
Bastiaan T. Heijmans
Affiliation:
Department of Molecular Epidemiology, Leiden University Medical Centre, Postbus 9600, 2300 RCLeiden, The Netherlands
Régine P. M. Steegers-Theunissen*
Affiliation:
Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands Department of Paediatrics, Division of Neonatology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CARotterdam, The Netherlands
*
Address for correspondence: Régine P. M. Steegers-Theunissen, MD, PhD, Professor in Periconception Epidemiology, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Postbus 2040, 3000 CA, Rotterdam, The Netherlands. Email: r.steegers@erasmusmc.nl
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Abstract

Epigenetic programming is essential for lineage differentiation, embryogenesis and placentation in early pregnancy. In epigenetic association studies, DNA methylation is often examined in DNA derived from white blood cells, although its validity to other tissues of interest remains questionable. Therefore, we investigated the tissue specificity of epigenome-wide DNA methylation in newborn and placental tissues. Umbilical cord white blood cells (UC-WBC, n = 25), umbilical cord blood mononuclear cells (UC-MNC, n = 10), human umbilical vein endothelial cells (HUVEC, n = 25) and placental tissue (n = 25) were obtained from 36 uncomplicated pregnancies. Genome-wide DNA methylation was measured by the Illumina HumanMethylation450K BeadChip. Using UC-WBC as a reference tissue, we identified 3595 HUVEC tissue-specific differentially methylated regions (tDMRs) and 11,938 placental tDMRs. Functional enrichment analysis showed that HUVEC and placental tDMRs were involved in embryogenesis, vascular development and regulation of gene expression. No tDMRs were identified in UC-MNC. In conclusion, the extensive amount of genome-wide HUVEC and placental tDMRs underlines the relevance of tissue-specific approaches in future epigenetic association studies, or the use of validated representative tissues for a certain disease of interest, if available. To this purpose, we herewith provide a relevant dataset of paired, tissue-specific, genome-wide methylation measurements in newborn tissues.

Keywords

EWAStissue specificityHUVECumbilical cord bloodplacenta
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 12 , Issue 1 , February 2021 , pp. 113 - 123
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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References

Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359(1), 61–73.Google ScholarPubMed
Senner, CE. The role of DNA methylation in mammalian development. Reprod Biomed Online. 2011; 22(6), 529–535.CrossRefGoogle ScholarPubMed
Koukoura, O, Sifakis, S, Spandidos, DA. DNA methylation in the human placenta and fetal growth (review). Mol Med Rep. 2012; 5(4), 883–889.Google Scholar
Mill, J, Heijmans, BT. From promises to practical strategies in epigenetic epidemiology. Nature Rev Genet. 2013; 14(8), 585–594.CrossRefGoogle ScholarPubMed
Gama-Sosa, MA, Midgett, RM, Slagel, VA, et al. Tissue-specific differences in DNA methylation in various mammals. Biochimica et Biophysica Acta. 1983; 740(2), 212–219.CrossRefGoogle ScholarPubMed
Herzog, E, Galvez, J, Roks, A, et al. Tissue-specific DNA methylation profiles in newborns. Clin Epigenetics. 2013; 5(1), 8.Google ScholarPubMed
Ollikainen, M, Smith, KR, Joo, EJ, et al. DNA methylation analysis of multiple tissues from newborn twins reveals both genetic and intrauterine components to variation in the human neonatal epigenome. Hum Mol Genet. 2010;19(21), 4176–4188.CrossRefGoogle ScholarPubMed
Lowe, R, Slodkowicz, G, Goldman, N, Rakyan, VK. The human blood DNA methylome displays a highly distinctive profile compared with other somatic tissues. Epigenetics. 2015; 10(4), 274–281.CrossRefGoogle ScholarPubMed
Slieker, RC, Bos, SD, Goeman, JJ, et al. Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450K array. Epigenetics Chromatin. 2013; 6(1), 26.CrossRefGoogle ScholarPubMed
Lokk, K, Modhukur, V, Rajashekar, B, et al. DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome Biology. 2014; 15(4), r54.CrossRefGoogle ScholarPubMed
Ma, B, Allard, C, Bouchard, L, et al. Locus-specific DNA methylation prediction in cord blood and placenta. Epigenetics. 2019; 14(4), 405–420.CrossRefGoogle ScholarPubMed
De Carli, MM, Baccarelli, AA, Trevisi, L, et al. Epigenome-wide cross-tissue predictive modeling and comparison of cord blood and placental methylation in a birth cohort. Epigenomics. 2017; 9(3), 231–240.Google Scholar
de Goede, OM, Lavoie, PM, Robinson, WP. Characterizing the hypomethylated DNA methylation profile of nucleated red blood cells from cord blood. Epigenomics. 2016; 8(11), 1481–1494.CrossRefGoogle ScholarPubMed
Roadmap Epigenomics, C, Kundaje, A, Meuleman, W, et al. Integrative analysis of 111 reference human epigenomes. Nature. 2015; 518(7539), 317–330.Google Scholar
Gomes, MV, Pelosi, GG. Epigenetic vulnerability and the environmental influence on health. Exp Biol Med (Maywood). 2013; 238(8), 859–865.CrossRefGoogle ScholarPubMed
Sandovici, I, Hoelle, K, Angiolini, E, Constancia, M. Placental adaptations to the maternal-fetal environment: implications for fetal growth and developmental programming. Reprod Biomed Online. 2012; 25(1), 68–89. doi: 10.1016/j.rbmo.2012.03.017.CrossRefGoogle ScholarPubMed
Casanello, P, Schneider, D, Herrera, EA, Uauy, R, Krause, BJ. Endothelial heterogeneity in the umbilico-placental unit: DNA methylation as an innuendo of epigenetic diversity. Front Pharmacol. 2014; 5, 49.CrossRefGoogle ScholarPubMed
Jin, SW, Patterson, C. The opening act: vasculogenesis and the origins of circulation. Arteriosclerosis, Thrombosis, and Vascular Biology. 2009; 29(5), 623–629.CrossRefGoogle ScholarPubMed
Krause, B, Sobrevia, L, Casanello, P. Epigenetics: new concepts of old phenomena in vascular physiology. Current Vascular Pharmacology. 2009; 7(4), 513–520.CrossRefGoogle ScholarPubMed
Koestler, DC, Christensen, B, Karagas, MR, et al. Blood-based profiles of DNA methylation predict the underlying distribution of cell types: a validation analysis. Epigenetics. 2013; 8(8), 816–826.CrossRefGoogle ScholarPubMed
Steegers-Theunissen, RP, Verheijden-Paulissen, JJ, van Uitert, EM, et al. Cohort profile: the Rotterdam periconceptional cohort (predict study). Int J Epidemiol. 2016; 45(2), 374–381.CrossRefGoogle Scholar
Dedeurwaerder, S, Defrance, M, Calonne, E, Denis, H, Sotiriou, C, Fuks, F. Evaluation of the Infinium Methylation 450K technology. Epigenomics. 2011; 3(6), 771–784.CrossRefGoogle ScholarPubMed
Sandoval, J, Heyn, H, Moran, S, et al. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome. Epigenetics. 2011; 6(6), 692–702.CrossRefGoogle ScholarPubMed
Bibikova, M, Barnes, B, Tsan, C, et al. High density DNA methylation array with single CpG site resolution. Genomics. 2011; 98(4), 288–295.CrossRefGoogle ScholarPubMed
Huber, W, Carey, VJ, Gentleman, R, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015; 12(2), 115–121.CrossRefGoogle ScholarPubMed
Pidsley, R, CC, YW, Volta, M, Lunnon, K, Mill, J, Schalkwyk, LC. A data-driven approach to preprocessing Illumina 450K methylation array data. BMC Genomics. 2013; 14, 293.CrossRefGoogle ScholarPubMed
Du, P, Zhang, X, Huang, CC, et al. Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics. 2010; 11, 587.CrossRefGoogle ScholarPubMed
Novakovic, B, Yuen, RK, Gordon, L, et al. Evidence for widespread changes in promoter methylation profile in human placenta in response to increasing gestational age and environmental/stochastic factors. BMC Genomics. 2011; 12, 529.CrossRefGoogle ScholarPubMed
Houseman, EA, Kile, ML, Christiani, DC, Ince, TA, Kelsey, KT, Marsit, CJ. Reference-free deconvolution of DNA methylation data and mediation by cell composition effects. BMC Bioinformatics. 2016; 17, 259.CrossRefGoogle ScholarPubMed
Marabita, F, Almgren, M, Lindholm, ME, et al. An evaluation of analysis pipelines for DNA methylation profiling using the Illumina HumanMethylation450 BeadChip platform. Epigenetics. 2013; 8(3), 333–346.CrossRefGoogle ScholarPubMed
Franzen, J, Zirkel, A, Blake, J, et al. Senescence-associated DNA methylation is stochastically acquired in subpopulations of mesenchymal stem cells. Aging Cell. 2017; 16(1), 183–191.Google ScholarPubMed
Paquette, AG, Houseman, EA, Green, BB, et al. Regions of variable DNA methylation in human placenta associated with newborn neurobehavior. Epigenetics. 2016; 11(8), 603–613.CrossRefGoogle ScholarPubMed
Slieker, RC, Roost, MS, van Iperen, L, et al. DNA Methylation Landscapes of Human Fetal Development. PLoS genetics. 2015; 11(10), e1005583.CrossRefGoogle ScholarPubMed
Bardou, P, Mariette, J, Escudie, F, Djemiel, C, Klopp, C. jvenn: an interactive Venn diagram viewer. BMC Bioinformatics. 2014; 15, 293.Google Scholar
Huang, W da, Sherman, BT, Lempicki, RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009; 37(1), 1–13.CrossRefGoogle Scholar
Huang, W da, Sherman, BT, Lempicki, RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols. 2009; 4(1), 44–57.CrossRefGoogle Scholar
Schroeder, DI, Blair, JD, Lott, P, et al. The human placenta methylome. Proc Natl Acad Sci U S A. 2013; 110(15), 6037–6042.Google ScholarPubMed
Bruce, M. Carlson, BC. Human Embryology and Developmental Biology, 2009. MOSBY.Google Scholar
Adamo, L, Garcia-Cardena, G. The vascular origin of hematopoietic cells. Dev Biol. 2012; 362(1), 1–10.Google ScholarPubMed
Lowe, R, Gemma, C, Beyan, H, et al. Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies. Epigenetics. 2013; 8(4), 445–454.CrossRefGoogle ScholarPubMed
Byun, HM, Siegmund, KD, Pan, F, et al. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet. 2009; 18(24), 4808–4817.CrossRefGoogle ScholarPubMed
Rakyan, VK, Down, TA, Thorne, NP, et al. An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res. 2008; 18(9), 1518–1529.CrossRefGoogle Scholar
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(19), e182–e189.CrossRefGoogle ScholarPubMed
Bakulski, KM, Feinberg, JI, Andrews, SV, et al. DNA methylation of cord blood cell types: Applications for mixed cell birth studies. Epigenetics. 2016; 11(5), 354–362.Google ScholarPubMed
Wu, HC, Delgado-Cruzata, L, Flom, JD, et al. Global methylation profiles in DNA from different blood cell types. Epigenetics. 2011; 6(1), 76–85.CrossRefGoogle ScholarPubMed
Jones, PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nature Rev Genet. 2012; 13(7), 484–492.CrossRefGoogle ScholarPubMed
Harper, KN, Peters, BA, Gamble, MV. Batch effects and pathway analysis: two potential perils in cancer studies involving DNA methylation array analysis. Cancer Epidemiol Biomarkers Prev.: A Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology. 2013; 22(6), 1052–1060.CrossRefGoogle ScholarPubMed
Grigoriu, A, Ferreira, JC, Choufani, S, Baczyk, D, Kingdom, J, Weksberg, R. Cell specific patterns of methylation in the human placenta. Epigenetics. 2011; 6(3), 368–379.CrossRefGoogle ScholarPubMed
Joo, JE, Hiden, U, Lassance, L, et al. Variable promoter methylation contributes to differential expression of key genes in human placenta-derived venous and arterial endothelial cells. BMC Genomics. 2013; 14, 475.CrossRefGoogle ScholarPubMed
Chen, YA, Lemire, M, Choufani, S, et al. Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics. 2013; 8(2), 203–209.Google ScholarPubMed
Cencioni, C, Spallotta, F, Martelli, F, et al. Oxidative stress and epigenetic regulation in ageing and age-related diseases. International Journal of Molecular Sciences. 2013; 14(9), 17643–17663.CrossRefGoogle ScholarPubMed
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