title: Genome-wide DNA methylation profiling identifies a folate-sensitive region of differential methylation upstream of ZFP57-imprinting regulator in humans.
abstract: Folate intake during pregnancy may affect the regulation of DNA methylation during fetal development. The genomic regions in the offspring that may be sensitive to folate exposure during in utero development have not been characterized. Using genome-scale profiling, we investigated DNA methylation in 2 immune cell types (CD4(+) and antigen-presenting cells) isolated from neonatal cord blood, selected on the basis of in utero folate exposure. High-folate (HF; n=11) and low-folate (LF; n=12) groups were selected from opposite extremes of maternal serum folate levels measured in the last trimester of pregnancy. A comparison of these groups revealed differential methylation at 7 regions across the genome. By far, the biggest effect observed was hypomethylation of a 923 bp region 3 kb upstream of the ZFP57 transcript, a regulator of DNA methylation during development, observed in both cell types. Levels of H3/H4 acetylation at ZFP57 promoter and ZFP57 mRNA expression were higher in CD4(+) cells in the HF group relative to the LF group. Hypomethylation at this region was replicated in an independent sample set. These data suggest that exposure to folate has effects on the regulation of DNA methylation during fetal development, and this may be important for health and disease.
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia;
authors.forename: Manori
authors.initials: M
authors.lastname: Amarasekera
authors.affiliation: Cancer and Disease Epigenetics Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia; Centre for Food and Allergy Research, Melbourne, Victoria, Australia;
authors.forename: David
authors.initials: D
authors.lastname: Martino
authors.affiliation: Cancer and Disease Epigenetics Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Institute for Medical Research, Monash University, Melbourne, Victoria, Australia;
authors.forename: Sarah
authors.initials: S
authors.lastname: Ashley
authors.affiliation: Institute of Laboratory Medicine, Pathobiochemistry, and Molecular Diagnostics, Philipps University, Marburg, Germany; and.
authors.forename: Hani
authors.initials: H
authors.lastname: Harb
authors.affiliation: Institute of Laboratory Medicine, Pathobiochemistry, and Molecular Diagnostics, Philipps University, Marburg, Germany; and.
authors.forename: Dörthe
authors.initials: D
authors.lastname: Kesper
authors.affiliation: Telethon Institute for Child Health Research, Perth, Western Australia, Australia.
authors.forename: Deborah
authors.initials: D
authors.lastname: Strickland
authors.affiliation: Cancer and Disease Epigenetics Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia;
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia; susan.prescott@uwa.edu.au.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Prescott
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D047109:Fetal Development / Q000235:genetics*; D005492:Folic Acid / Q000378:metabolism*; D020869:Gene Expression Profiling; D015894:Genome, Human; D018392:Genomic Imprinting; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D011247:Pregnancy; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C531063:ZFP57 protein, human; D005492:Folic Acid
keywords: T cells; antigen-presenting cells; developmental programming; epigenetics; neonate