title: Variable promoter methylation contributes to differential expression of key genes in human placenta-derived venous and arterial endothelial cells.
abstract: BACKGROUND
  The endothelial compartment, comprising arterial, venous and lymphatic cell types, is established prenatally in association with rapid phenotypic and functional changes. The molecular mechanisms underpinning this process in utero have yet to be fully elucidated. The aim of this study was to investigate the potential for DNA methylation to act as a driver of the specific gene expression profiles of arterial and venous endothelial cells.
  
  
  RESULTS
  Placenta-derived venous and arterial endothelial cells were collected at birth prior to culturing. DNA methylation was measured at >450,000 CpG sites in parallel with expression measurements taken from 25,000 annotated genes. A consistent set of genomic loci was found to show coordinate differential methylation between the arterial and venous cell types. This included many loci previously not investigated in relation to endothelial function. An inverse relationship was observed between gene expression and promoter methylation levels for a limited subset of genes implicated in endothelial function, including NOS3, encoding endothelial Nitric Oxide Synthase.
  
  
  CONCLUSIONS
  Endothelial cells derived from the placental vasculature at birth contain widespread methylation of key regulatory genes. These are candidates involved in the specification of different endothelial cell types and represent potential target genes for environmentally mediated epigenetic disruption in utero in association with cardiovascular disease risk later in life.
authors.affiliation: Cancer and Disease Epigenetics, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Australia.
authors.forename: Jihoon E
authors.initials: JE
authors.lastname: Joo
authors.forename: Ursula
authors.initials: U
authors.lastname: Hiden
authors.forename: Luciana
authors.initials: L
authors.lastname: Lassance
authors.forename: Lavinia
authors.initials: L
authors.lastname: Gordon
authors.forename: David J
authors.initials: DJ
authors.lastname: Martino
authors.forename: Gernot
authors.initials: G
authors.lastname: Desoye
authors.forename: Richard
authors.initials: R
authors.lastname: Saffery
mesh_terms: D001158:Arteries / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D059467:Transcriptome; D014680:Veins / Q000166:cytology*
chemical_list: D035683:MicroRNAs