title: DNA methylation at the Igf2/H19 imprinting control region is associated with cerebellum mass in outbred mice.
abstract: BACKGROUND
  Insulin-like growth factor 2 (Igf2) is a paternally expressed imprinted gene regulating fetal growth, playing an integral role in the development of many tissues including the brain. The parent-of-origin specific expression of Igf2 is largely controlled by allele-specific DNA methylation at CTCF-binding sites in the imprinting control region (ICR), located immediately upstream of the neighboring H19 gene. Previously we reported evidence of a negative correlation between DNA methylation in this region and cerebellum weight in humans.
  
  
  RESULTS
  We quantified cerebellar DNA methylation across all four CTCF binding sites spanning the murine Igf2/H19 ICR in an outbred population of Heterogeneous Stock (HS) mice (n = 48). We observe that DNA methylation at the second and third CTCF binding sites in the Igf2/H19 ICR shows a negative relationship with cerebellar mass, reflecting the association observed in human post-mortem cerebellum tissue.
  
  
  CONCLUSIONS
  Given the important role of the cerebellum in motor control and cognition, and the link between structural cerebellar abnormalities and neuropsychiatric phenotypes, the identification of epigenetic factors associated with cerebellum growth and development may provide important insights about the etiology of psychiatric disorders.
authors.affiliation: Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE5 8AF, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pidsley
authors.forename: Cathy
authors.initials: C
authors.lastname: Fernandes
authors.forename: Joana
authors.initials: J
authors.lastname: Viana
authors.forename: Jose L
authors.initials: JL
authors.lastname: Paya-Cano
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Smith
authors.forename: Leonard C
authors.initials: LC
authors.lastname: Schalkwyk
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
mesh_terms: D000483:Alleles; D000818:Animals; D021461:Animals, Outbred Strains; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002531:Cerebellum / Q000033:anatomy & histology* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D056426:Genetic Loci; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D019901:Locus Control Region / Q000235:genetics*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; C000619698:Ctcf protein, mouse; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D007335:Insulin-Like Growth Factor II