Allele-specific enhancer interaction at the Peg3 imprinted domain.

The parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal...

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Main Authors: Joomyeong Kim, Wesley D Frey, Kaustubh Sharma, Subash Ghimire, Ryoichi Teruyama, Lisa Stubbs
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2019-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0224287
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author Joomyeong Kim
Wesley D Frey
Kaustubh Sharma
Subash Ghimire
Ryoichi Teruyama
Lisa Stubbs
author_facet Joomyeong Kim
Wesley D Frey
Kaustubh Sharma
Subash Ghimire
Ryoichi Teruyama
Lisa Stubbs
author_sort Joomyeong Kim
collection DOAJ
description The parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal-to-maternal expression for Peg3 and the maternal-to-paternal expression for Zim1. The expression levels of Peg3 and Zim1, but not the spatial expression patterns, within the brain showed clear differences between wild type and mutant animals. We identified putative enhancers localized upstream of Peg3 that displayed allele-biased DNA methylation, and that also participate in allele-biased chromosomal conformations with regional promoters. Most importantly, these data suggest for the first time that long-distance enhancers may contribute to allelic expression within imprinted domains through allele-biased interactions with regional promoters.
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spelling doaj.art-d9ef7bb89b9f4676876ce3a162e53c2f2022-12-21T18:25:31ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022428710.1371/journal.pone.0224287Allele-specific enhancer interaction at the Peg3 imprinted domain.Joomyeong KimWesley D FreyKaustubh SharmaSubash GhimireRyoichi TeruyamaLisa StubbsThe parental allele specificity of mammalian imprinted genes has been evolutionarily well conserved, although its functional constraints and associated mechanisms are not fully understood. In the current study, we generated a mouse mutant with switched active alleles driving the switch from paternal-to-maternal expression for Peg3 and the maternal-to-paternal expression for Zim1. The expression levels of Peg3 and Zim1, but not the spatial expression patterns, within the brain showed clear differences between wild type and mutant animals. We identified putative enhancers localized upstream of Peg3 that displayed allele-biased DNA methylation, and that also participate in allele-biased chromosomal conformations with regional promoters. Most importantly, these data suggest for the first time that long-distance enhancers may contribute to allelic expression within imprinted domains through allele-biased interactions with regional promoters.https://doi.org/10.1371/journal.pone.0224287
spellingShingle Joomyeong Kim
Wesley D Frey
Kaustubh Sharma
Subash Ghimire
Ryoichi Teruyama
Lisa Stubbs
Allele-specific enhancer interaction at the Peg3 imprinted domain.
PLoS ONE
title Allele-specific enhancer interaction at the Peg3 imprinted domain.
title_full Allele-specific enhancer interaction at the Peg3 imprinted domain.
title_fullStr Allele-specific enhancer interaction at the Peg3 imprinted domain.
title_full_unstemmed Allele-specific enhancer interaction at the Peg3 imprinted domain.
title_short Allele-specific enhancer interaction at the Peg3 imprinted domain.
title_sort allele specific enhancer interaction at the peg3 imprinted domain
url https://doi.org/10.1371/journal.pone.0224287
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