An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity.
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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2012-01-01
|
Series: | PLoS Genetics |
Online Access: | http://europepmc.org/articles/PMC3305357?pdf=render |
id |
doaj-491cd0058c6d4ad6bbd00cb3104365a5 |
---|---|
record_format |
Article |
spelling |
doaj-491cd0058c6d4ad6bbd00cb3104365a52020-11-24T22:20:29ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042012-01-0183e100254310.1371/journal.pgen.1002543An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity.Peter KuehnenMona MischkeSusanna WiegandChristine SersBernhard HorsthemkeSusanne LauThomas KeilYoung-Ae LeeAnnette GruetersHeiko KrudeThe 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.http://europepmc.org/articles/PMC3305357?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Peter Kuehnen Mona Mischke Susanna Wiegand Christine Sers Bernhard Horsthemke Susanne Lau Thomas Keil Young-Ae Lee Annette Grueters Heiko Krude |
spellingShingle |
Peter Kuehnen Mona Mischke Susanna Wiegand Christine Sers Bernhard Horsthemke Susanne Lau Thomas Keil Young-Ae Lee Annette Grueters Heiko Krude An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. PLoS Genetics |
author_facet |
Peter Kuehnen Mona Mischke Susanna Wiegand Christine Sers Bernhard Horsthemke Susanne Lau Thomas Keil Young-Ae Lee Annette Grueters Heiko Krude |
author_sort |
Peter Kuehnen |
title |
An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. |
title_short |
An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. |
title_full |
An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. |
title_fullStr |
An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. |
title_full_unstemmed |
An Alu element-associated hypermethylation variant of the POMC gene is associated with childhood obesity. |
title_sort |
alu element-associated hypermethylation variant of the pomc gene is associated with childhood obesity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2012-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3305357?pdf=render |
work_keys_str_mv |
AT peterkuehnen analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT monamischke analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT susannawiegand analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT christinesers analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT bernhardhorsthemke analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT susannelau analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT thomaskeil analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT youngaelee analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT annettegrueters analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT heikokrude analuelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT peterkuehnen aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT monamischke aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT susannawiegand aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT christinesers aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT bernhardhorsthemke aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT susannelau aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT thomaskeil aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT youngaelee aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT annettegrueters aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity AT heikokrude aluelementassociatedhypermethylationvariantofthepomcgeneisassociatedwithchildhoodobesity |
_version_ |
1725775008357154816 |