title: Placental 5-methylcytosine and 5-hydroxymethylcytosine patterns associate with size at birth.
abstract: Altered placental function as a consequence of aberrant imprinted gene expression may be one mechanism mediating the association between low birth weight and increased cardiometabolic disease risk. Imprinted gene expression is regulated by epigenetic mechanisms, particularly DNA methylation (5mC) at differentially methylated regions (DMRs). While 5-hydroxymethylcytosine (5hmC) is also present at DMRs, many techniques do not distinguish between 5mC and 5hmC. Using human placental samples, we show that the expression of the imprinted gene CDKN1C associates with birth weight. Using specific techniques to map 5mC and 5hmC at DMRs controlling the expression of CDKN1C and the imprinted gene IGF2, we show that 5mC enrichment at KvDMR and DMR0, and 5hmC enrichment within the H19 gene body, associate positively with birth weight. Importantly, the presence of 5hmC at imprinted DMRs may complicate the interpretation of DNA methylation studies in placenta; future studies should consider using techniques that distinguish between, and permit quantification of, both modifications.
authors.affiliation: a University/British Heart Foundation Center for Cardiovascular Science; University of Edinburgh; The Queen's Medical Research Institute ; Edinburgh , UK.
authors.forename: Chinthika
authors.initials: C
authors.lastname: Piyasena
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Reynolds
authors.forename: Batbayar
authors.initials: B
authors.lastname: Khulan
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
authors.forename: Gopi
authors.initials: G
authors.lastname: Menon
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Drake
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D001724:Birth Weight / Q000235:genetics; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000096:biosynthesis* / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; C035170:IGF2 protein, human; C011865:5-hydroxymethylcytosine; D007335:Insulin-Like Growth Factor II; D044503:5-Methylcytosine; D003596:Cytosine
keywords: 5-hydroxymethylcytosine; 5-methylcytosine; Placenta; birth weight; imprinted gene