title: An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity.
abstract: The individual risk for common diseases not only depends on genetic but also on epigenetic polymorphisms. To assess the role of epigenetic variations in the individual risk for obesity, we have determined the methylation status of two CpG islands at the POMC locus in obese and normal-weight children. We found a hypermethylation variant targeting individual CpGs at the intron 2-exon 3 boundary of the POMC gene by bisulphite sequencing that was significantly associated with obesity. POMC exon 3 hypermethylation interferes with binding of the transcription enhancer P300 and reduces expression of the POMC transcript. Since intron 2 contains Alu elements that are known to influence methylation in their genomic vicinity, the exon 3 methylation variant seems to result from an Alu element-triggered default state of methylation boundary definition. Exon 3 hypermethylation in the POMC locus represents the first identified DNA methylation variant that is associated with the individual risk for obesity.
authors.affiliation: Institut für Experimentelle Pädiatrische Endokrinologie, Charité - Universitätsmedizin Berlin, Berlin, Germany. peter.kuehnen@charite.de
authors.forename: Peter
authors.initials: P
authors.lastname: Kuehnen
authors.forename: Mona
authors.initials: M
authors.lastname: Mischke
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.forename: Christine
authors.initials: C
authors.lastname: Sers
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Susanne
authors.initials: S
authors.lastname: Lau
authors.forename: Thomas
authors.initials: T
authors.lastname: Keil
authors.forename: Young-Ae
authors.initials: YA
authors.lastname: Lee
authors.forename: Annette
authors.initials: A
authors.lastname: Grueters
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
mesh_terms: D000293:Adolescent; D020087:Alu Elements / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic; D011323:Primates / Q000235:genetics; D011333:Pro-Opiomelanocortin / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors
chemical_list: D011333:Pro-Opiomelanocortin