期刊论文详细信息
Clinical Epigenetics
Tissue-specific DNA methylation profiles in newborns
Régine Steegers-Theunissen1  Eric Steegers4  Jan Cornelissen5  Paul Eilers6  Michael Verbiest2  Lisette Stolk2  Anton Roks3  Jubby Galvez4  Emilie Herzog4 
[1] Department of Clinical Genetics, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands;Department of Internal Medicine, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands;Department of Internal Medicine, Section of Vascular Medicine and Pharmacology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands;Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands;Department of Haematology, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands;Department of Biostatistics, Erasmus MC, University Medical Centre Rotterdam, dr. Molewaterplein 50, Rotterdam, GE 3015, the Netherlands
关键词: IGF2/H19;    Placenta;    Wharton jelly;    Umbilical cord blood;    Epigenetics;   
Others  :  790993
DOI  :  10.1186/1868-7083-5-8
 received in 2013-03-15, accepted in 2013-05-24,  发布年份 2013
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【 摘 要 】

Background

Epidemiological studies demonstrate that foetal growth restriction and low birth weight affect long-term health. Derangements in tissue-specific epigenetic programming of foetal and placental tissues are a suggested underlying mechanism of which DNA methylation is best understood. DNA methylation has been mostly investigated in DNA from white blood cells. To improve baseline understanding of tissue-specific DNA methylation, we examined variation in DNA methylation profiles of the imprinted foetal growth genes IGF2 and H19 in three different tissues from the same newborn obtained at the same time.

Findings

We obtained DNA from umbilical cord blood mononuclear cells (MNC; CD34+ and CD34, n = 6), foetal side of the placenta (n = 5) and umbilical cord Wharton jelly (n = 5). DNA methylation of the IGF2 differentially methylated region (DMR) and H19 DMR was measured using quantitative mass spectrometry. Analysis of variance testing showed no statistical difference between total mean methylation of CD34+ and CD34 MNC. Further comparisons were made with the pooled total MNC fraction. Mean IGF2 DMR methylation of Wharton jelly was 1.3 times higher (P = 0.001) than mean methylation of the pooled MNC. Placental mean methylation was 0.8 times lower (P <0.001) and Wharton jelly 0.9 times lower (P <0.001) than the pooled MNC of H19 DMR.

Conclusion

The total MNC fraction is a rather homogeneous cell population for methylation studies of imprinted genes in umbilical cord blood white blood cells, but may not always reflect the methylation levels of IGF2 and H19 in other organs.

【 授权许可】

   
2013 Herzog et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Hanson MA, Gluckman PD: Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol 2008, 102:90-93.
  • [2]Ollikainen M, Smith KR, Joo EJ, Ng HK, Andronikos R, Novakovic B, Abdul Aziz NK, Carlin JB, Morley R, Saffery R, Craig JM: 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, 19:4176-4188.
  • [3]Godfrey KM, Sheppard A, Gluckman PD, Lillycrop KA, Burdge GC, McLean C, Rodford J, Slater-Jefferies JL, Garratt E, Crozier SR, Emerald BS, Gale CR, Inskip HM, Cooper C, Hanson MA: Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 2011, 60:1528-1534.
  • [4]Rakyan VK, Down TA, Thorne NP, Flicek P, Kulesha E, Graf S, Tomazou EM, Backdahl L, Johnson N, Herberth M, Howe KL, Jackson DK, Miretti MM, Fiegler H, Marioni JC, Birney E, Hubbard TJ, Carter NP, Tavaré S, Beck S: An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Res 2008, 18:1518-1529.
  • [5]Ghosh S, Yates AJ, Fruhwald MC, Miecznikowski JC, Plass C, Smiraglia D: Tissue specific DNA methylation of CpG islands in normal human adult somatic tissues distinguishes neural from non-neural tissues. Epigenetics 2010, 5:527-538.
  • [6]Khavari DA, Sen GL, Rinn JL: DNA methylation and epigenetic control of cellular differentiation. Cell Cycle 2010, 9:3880-3883.
  • [7]Bird A: DNA methylation patterns and epigenetic memory. Genes Dev 2002, 16:6-21.
  • [8]Rugg-Gunn PJ: Epigenetic features of the mouse trophoblast. Reprod Biomed Online 2012, 25:21-30.
  • [9]Tabano S, Colapietro P, Cetin I, Grati FR, Zanutto S, Mando C, Antonazzo P, Pileri P, Rossella F, Larizza L, Sirchia SM, Miozzo M: Epigenetic modulation of the IGF2/H19 imprinted domain in human embryonic and extra-embryonic compartments and its possible role in fetal growth restriction. Epigenetics 2010, 5:313-324.
  • [10]Prickett AR, Oakey RJ: A survey of tissue-specific genomic imprinting in mammals. Mol Genet Genomics 2012, 287:621-630.
  • [11]Vu TH, Li T, Nguyen D, Nguyen BT, Yao XM, Hu JF, Hoffman AR: Symmetric and asymmetric DNA methylation in the human IGF2-H19 imprinted region. Genomics 2000, 64:132-143.
  • [12]Angiolini E, Fowden A, Coan P, Sandovici I, Smith P, Dean W, Burton G, Tycko B, Reik W, Sibley C, Constancia M: Regulation of placental efficiency for nutrient transport by imprinted genes. Placenta 2006, 27(Suppl A):98-102.
  • [13]Constancia M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, Stewart F, Kelsey G, Fowden A, Sibley C, Reik W: Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 2002, 417:945-948.
  • [14]Junek T, Baum O, Lauter H, Vetter K, Matejevic D, Graf R: Pre-eclampsia associated alterations of the elastic fibre system in umbilical cord vessels. Anat Embryol (Berl) 2000, 201:291-303.
  • [15]Blanco MV, Vega HR, Giuliano R, Grana DR, Azzato F, Lerman J, Milei J: Histomorphometry of umbilical cord blood vessels in preeclampsia. J Clin Hypertens (Greenwich) 2011, 13:30-34.
  • [16]Inan S, Sanci M, Can D, Vatansever S, Oztekin O, Tinar S: Comparative morphological differences between umbilical cords from chronic hypertensive and preeclamptic pregnancies. Acta Med Okayama 2002, 56:177-186.
  • [17]Nelissen EC, van Montfoort AP, Dumoulin JC, Evers JL: Epigenetics and the placenta. Hum Reprod Update 2011, 17:397-417.
  • [18]Heijmans BT, Kremer D, Tobi EW, Boomsma DI, Slagboom PE: Heritable rather than age-related environmental and stochastic factors dominate variation in DNA methylation of the human IGF2/H19 locus. Hum Mol Genet 2007, 16:547-554.
  • [19]Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den Boom D: Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci U S A 2005, 102:15785-15790.
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