Email updates

Keep up to date with the latest news and content from Molecular Brain and BioMed Central.

Open Access Research

DNA methylation at the Igf2/H19 imprinting control region is associated with cerebellum mass in outbred mice

Ruth Pidsley1, Cathy Fernandes1, Joana Viana1, Jose L Paya-Cano1, Lin Liu1, Rebecca G Smith1, Leonard C Schalkwyk1 and Jonathan Mill12*

Author Affiliations

1 Institute of Psychiatry, King’s College London, De Crespigny Park, Denmark Hill, London, SE5 8AF, UK

2 University of Exeter Medical School, University of Exeter, Magdalen Road, Exeter, EX1 2LU, UK

For all author emails, please log on.

Molecular Brain 2012, 5:42  doi:10.1186/1756-6606-5-42

Published: 6 December 2012

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.

Keywords:
Igf2; H19; Epigenetics; DNA methylation; Cerebellum; Brain; Mouse; Genotype; Genomic imprinting