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

• Published in: Molecular brain Vol. 5; no. 1; p. 42
• Main Authors: Pidsley, Ruth, Fernandes, Cathy, Viana, Joana, Paya-Cano, Jose L, Liu, Lin, Smith, Rebecca G, Schalkwyk, Leonard C, Mill, Jonathan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06-12-2012; BioMed Central; BMC
• Subjects: Alleles; Animals; Animals, Outbred Strains; Binding Sites; Book publishing; Brain; CCCTC-Binding Factor; Cerebellum; Cerebellum - anatomy & histology; Cerebellum - metabolism; Cognition; CpG Islands - genetics; Deoxyribonucleic acid; DNA; DNA methylation; DNA Methylation - genetics; Epigenetic inheritance; Epigenetics; Etiology; Fetus; Fetuses; Genes; Genetic Loci; Genetics; Genomes; Genomic imprinting; Genomic Imprinting - genetics; Genotype; Genotype & phenotype; Growth; H19; H19 gene; Humans; Igf2; Imprinting; Insulin; Insulin-like growth factor II; Insulin-Like Growth Factor II - genetics; Insulin-like growth factors; Locus Control Region - genetics; Male; Mental disorders; Methylation; Mice; Motor task performance; Mouse; Organ Size - genetics; Protein binding; Regression analysis; Repressor Proteins - metabolism; RNA, Long Noncoding - genetics; United Kingdom
• ISSN: 1756-6606; 1756-6606
• DOI: 10.1186/1756-6606-5-42

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.
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.
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.