title: The promoter methylomes of monochorionic twin placentas reveal intrauterine growth restriction-specific variations in the methylation patterns.
abstract: Intrauterine growth restriction (IUGR) affects the foetus and has a number of pathological consequences throughout life. Recent work has indicated that variations in DNA methylation might cause placental dysfunction, which may be associated with adverse pregnancy complications. Here, we investigated the promoter methylomes of placental shares from seven monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR) using the healthy twin as an ideal control. Our work demonstrated that the IUGR placental shares harboured a distinct DNA hypomethylation pattern and that the methylation variations preferentially occurred in CpG island shores or non-CpG island promoters. The differentially methylated promoters could significantly separate the IUGR placental shares from the healthy ones. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) further confirmed the genome-wide DNA hypomethylation and the lower level of hydroxymethylation statuses in the IUGR placental shares. The methylation variations of the LRAT and SLC19A1 promoters, which are involved in vitamin A metabolism and folate transportation, respectively, and the EFS promoter were further validated in an additional 12 pairs of MC twins with sIUGR. Although the expressions of LRAT, SLC19A1 and EFS were not affected, we still speculated that DNA methylation and hydroxymethylation might serve a functional role during in utero foetal development.
authors.affiliation: Foetal Medicine Centre, Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: He
authors.affiliation: Science &Technology Department, BGI-Shenzhen, No.11, Bei Shan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Hanlin
authors.initials: H
authors.lastname: Lu
authors.affiliation: Science &Technology Department, BGI-Shenzhen, No.11, Bei Shan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Luo
authors.affiliation: Science &Technology Department, BGI-Shenzhen, No.11, Bei Shan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Science &Technology Department, BGI-Shenzhen, No.11, Bei Shan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynaecology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510655, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Foetal Medicine Centre, Department of Obstetrics and Gynaecology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Science &Technology Department, BGI-Shenzhen, No.11, Bei Shan Industrial Zone, Yantian District, Shenzhen 518083, China.
authors.forename: Junwen
authors.initials: J
authors.lastname: Wang
mesh_terms: D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D005333:Fetus / Q000473:pathology; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*
references.citation: J Clin Pathol. 2008 Dec;61(12):1296-302
references.pmid: 18755720
references.citation: J Biol Chem. 1999 Feb 5;274(6):3834-41
references.pmid: 9920938
references.citation: Nat Genet. 2009 Feb;41(2):240-5
references.pmid: 19151718
references.citation: Pediatr Endocrinol Rev. 2009 Feb;6 Suppl 3:332-6
references.pmid: 19404231
references.citation: Science. 2009 May 15;324(5929):930-5
references.pmid: 19372391
references.citation: Science. 2009 May 15;324(5929):929-30
references.pmid: 19372393
references.citation: Am J Reprod Immunol. 2009 Aug;62(2):78-89
references.pmid: 19614624
references.citation: BMC Bioinformatics. 2009;10:232
references.pmid: 19635165
references.citation: Nat Genet. 2009 Dec;41(12):1350-3
references.pmid: 19881528
references.citation: PLoS One. 2010;5(1):e8888
references.pmid: 20126651
references.citation: J Nutr. 2010 Mar;140(3):437-45
references.pmid: 20071652
references.citation: Eur J Hum Genet. 2010 Jun;18(6):648-55
references.pmid: 20104244
references.citation: Eur J Hum Genet. 2010 Sep;18(9):1006-12
references.pmid: 20442742
references.citation: Epigenetics. 2011 Feb;6(2):247-55
references.pmid: 20962579
references.citation: Hum Reprod Update. 2011 May-Jun;17(3):397-417
references.pmid: 20959349
references.citation: Genes Dev. 2011 May 15;25(10):1010-22
references.pmid: 21576262
references.citation: Nature. 2011 May 19;473(7347):394-7
references.pmid: 21552279
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17253-60
references.pmid: 23045638
references.citation: Epigenomics. 2012 Oct;4(5):561-9
references.pmid: 23130837
references.citation: BMC Genomics. 2013;14:11
references.pmid: 23324053
references.citation: Prenat Diagn. 2013 May;33(5):484-91
references.pmid: 23529764
references.citation: PLoS One. 2013;8(5):e62969
references.pmid: 23667551
references.citation: Physiol Genomics. 2013 Jul 15;45(14):565-76
references.pmid: 23695884
references.citation: Mol Hum Reprod. 2013 Oct;19(10):697-708
references.pmid: 23770704
references.citation: Mol Hum Reprod. 2013 Nov;19(11):764-72
references.pmid: 23832168
references.citation: Exp Dermatol. 2013 Nov;22(11):757-9
references.pmid: 24433184
references.citation: Fetal Diagn Ther. 2014;36(2):86-98
references.pmid: 24457811
references.citation: Stem Cell Reports. 2014 Sep 9;3(3):432-43
references.pmid: 25241742
references.citation: J Assist Reprod Genet. 2014 Oct;31(10):1361-8
references.pmid: 24986528
references.citation: Med Oncol. 2014 Nov;31(11):254
references.pmid: 25260806
references.citation: Hum Mol Genet. 2014 Dec 1;23(23):6275-85
references.pmid: 24993786
references.citation: Placenta. 2015 Mar;36(3):297-303
references.pmid: 25573093
references.citation: Technol Cancer Res Treat. 2015 Aug;14(4):383-94
references.pmid: 26269607
references.citation: Mol Med. 2002 Jan;8(1):56-64
references.pmid: 11984006
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Am J Obstet Gynecol. 2004 Aug;191(2):481-7
references.pmid: 15343225
references.citation: Epigenetics. 2011 Jul;6(7):920-7
references.pmid: 21758004
references.citation: Int J Mol Med. 2011 Oct;28(4):481-7
references.pmid: 21805044
references.citation: BMC Cancer. 2011;11:380
references.pmid: 21871071
references.citation: Oncotarget. 2011 Aug;2(8):627-37
references.pmid: 21896958
references.citation: Physiol Genomics. 2011 Oct 20;43(20):1160-9
references.pmid: 21828247
references.citation: Reprod Sci. 2011 Nov;18(11):1111-7
references.pmid: 21693779
references.citation: Epigenomics. 2010 Oct;2(5):627-38
references.pmid: 22122048
references.citation: Mol Med Rep. 2012 Apr;5(4):883-9
references.pmid: 22294146
references.citation: J Clin Endocrinol Metab. 2012 Mar;97(3):689-95
references.pmid: 22238390
references.citation: BMC Genomics. 2011;12:597
references.pmid: 22151801
references.citation: Genome Res. 2012 Aug;22(8):1395-406
references.pmid: 22800725
references.citation: Ultrasound Obstet Gynecol. 1996 Jun;7(6):421-3
references.pmid: 8807758
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W741-8
references.pmid: 15980575
references.citation: Placenta. 2005 Sep-Oct;26(8-9):601-7
references.pmid: 16085039
references.citation: Nat Rev Genet. 2005 Aug;6(8):597-610
references.pmid: 16136652
references.citation: Bioinformatics. 2006 Jun 15;22(12):1540-2
references.pmid: 16595560
references.citation: Nat Rev Genet. 2007 Jan;8(1):71-7
references.pmid: 17146468
references.citation: Nat Genet. 2007 Apr;39(4):457-66
references.pmid: 17334365
references.citation: Ultrasound Obstet Gynecol. 2007 Jul;30(1):28-34
references.pmid: 17542039
references.citation: Placenta. 2007 Aug-Sep;28(8-9):803-11
references.pmid: 17509679
references.citation: Nucleic Acids Res. 1983 May 25;11(10):3087-95
references.pmid: 6856456
references.citation: Cell. 2012 Sep 14;150(6):1135-46
references.pmid: 22980977
references.citation: Obstet Gynecol. 1998 Jun;91(6):917-24
references.pmid: 9610996
references.citation: Nat Genet. 2009 Feb;41(2):178-86
references.pmid: 19151715