title: DNA hypermethylation of CD3(+) T cells from cord blood of infants exposed to intrauterine growth restriction.
abstract: Intrauterine growth restriction (IUGR) is associated with increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the mechanisms underlying the developmental origins of metabolic disease are poorly understood, evidence suggests that epigenomic alterations play a critical role. We sought to identify changes in DNA methylation patterns that are associated with IUGR in CD3(+) T cells purified from umbilical cord blood obtained from male newborns who were appropriate for gestational age (AGA) or who had been exposed to IUGR.
  
  
  
  CD3(+) T cells were isolated from cord blood obtained from IUGR and AGA infants. The genome-wide methylation profile in eight AGA and seven IUGR samples was determined using the HELP tagging assay. Validation analysis using targeted bisulfite sequencing and bisulfite massARRAY was performed on the original cohort as well as biological replicates consisting of two AGA and four IUGR infants. The Segway algorithm was used to identify methylation changes within regulatory regions of the genome.
  
  
  
  A global shift towards hypermethylation in IUGR was seen compared with AGA (89.8% of 4,425 differentially methylated loci), targeted to regulatory regions of the genome, specifically promoters and enhancers. Pathway analysis identified dysregulation of pathways involved in metabolic disease (type 2 diabetes mellitus, insulin signalling, mitogen-activated protein kinase signalling) and T cell development, regulation and activation (T cell receptor signalling), as well as transcription factors (TCF3, LEF1 and NFATC) that regulate T cells. Furthermore, bump-hunting analysis revealed differentially methylated regions in PRDM16 and HLA-DPB1, genes important for adipose tissue differentiation, stem cell maintenance and function and T cell activation.
  
  
  
  Our findings suggest that the alterations in methylation patterns observed in IUGR CD3(+) T cells may have functional consequences in targeted genes, regulatory regions and transcription factors. These may serve as biomarkers to identify those at 'high risk' for diminished attainment of full health potential who can benefit from early interventions.
  
  
  
  HELP tagging data: Gene Expression Omnibus database (GSE77268), scheduled to be released on 25 January 2019.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Rm F312, Bronx, NY, 10461, USA.
authors.forename: Lyda
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Rm F312, Bronx, NY, 10461, USA.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Seki
authors.affiliation: Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Fabien
authors.initials: F
authors.lastname: Delahaye
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Rm F312, Bronx, NY, 10461, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Mamta
authors.initials: M
authors.lastname: Fuloria
authors.affiliation: Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Francine
authors.initials: F
authors.lastname: Hughes Einstein
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Rm F312, Bronx, NY, 10461, USA. maureen.charron@einstein.yu.edu.|Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA. maureen.charron@einstein.yu.edu.|Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY, USA. maureen.charron@einstein.yu.edu.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism*; D002478:Cells, Cultured; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D005317:Fetal Growth Retardation / Q000235:genetics / Q000378:metabolism*; D005865:Gestational Age; D059868:HLA-DP beta-Chains / Q000378:metabolism; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D011247:Pregnancy; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D017252:CD3 Complex; D004268:DNA-Binding Proteins; D059868:HLA-DP beta-Chains; D051821:Lymphoid Enhancer-Binding Factor 1; D050778:NFATC Transcription Factors; D014157:Transcription Factors; C071170:HLA-DPB1 antigen; C497573:LEF1 protein, human; C494003:NFATC1 protein, human; C416371:PRDM16 protein, human; C407909:TCF3 protein, human
keywords: Human; Metabolic syndrome; Prediction of type 2 diabetes