Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta

Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These genes are known to be critical for placental development and fetal growth in mammals. Aberrant epigenetic profiles at imprinted loci, such as DNA methylation defects, are...

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Autores: Iglesias-Platas I, Martin-Trujillo A, Petazzi P, Guillaumet-Adkins A, Esteller M, Monk D
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p6554
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6554
Access Level:acceso abierto
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spelling Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placentaIglesias-Platas IMartin-Trujillo APetazzi PGuillaumet-Adkins AEsteller MMonk DGenomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These genes are known to be critical for placental development and fetal growth in mammals. Aberrant epigenetic profiles at imprinted loci, such as DNA methylation defects, are surprisingly rare in pregnancies with compromised fetal growth, while variations in transcriptional output from the expressed alleles of imprinted genes are more commonly reported in pregnancies complicated with intrauterine growth restriction (IUGR). To determine if PLAGL1 and HYMAI, two imprinted transcripts deregulated in Transient Neonatal Diabetes Mellitus, are involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. This revealed that despite appropriate maternal methylation at the shared PLAGL1/HYMAI promoter, there was a loss of correlation between PLAGL1 and HYMAI expression in IUGR. This incongruity was due to higher HYMAI expression in IUGR gestations, coupled with PLAGL1 down-regulation in placentas from IUGR girls, but not boys. The PLAGL1 protein is a zinc-finger transcription factor that has been shown to be a master coordinator of a genetic growth network in mice. We observe PLAGL1 binding to the H19/IGF2 shared enhancers in placentae, with significant correlations between PLAGL1 levels with H19 and IGF2 expression levels. In addition, PLAGL1 binding and expression also correlate with expression levels of metabolic regulator genes SLC2A4, TCF4 and PPAR gamma 1. Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta.OXFORD UNIV PRESS2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6554HUMAN MOLECULAR GENETICSISSN: 09646906ISSNe: 14602083reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p65542026-05-27T12:37:41Z
dc.title.none.fl_str_mv Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
title Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
spellingShingle Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
Iglesias-Platas I
title_short Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
title_full Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
title_fullStr Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
title_full_unstemmed Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
title_sort Altered expression of the imprinted transcription factor PLAGL1 deregulates a network of genes in the human IUGR placenta
dc.creator.none.fl_str_mv Iglesias-Platas I
Martin-Trujillo A
Petazzi P
Guillaumet-Adkins A
Esteller M
Monk D
author Iglesias-Platas I
author_facet Iglesias-Platas I
Martin-Trujillo A
Petazzi P
Guillaumet-Adkins A
Esteller M
Monk D
author_role author
author2 Martin-Trujillo A
Petazzi P
Guillaumet-Adkins A
Esteller M
Monk D
author2_role author
author
author
author
author
description Genomic imprinting is the epigenetic process that results in monoallelic expression of genes depending on parental origin. These genes are known to be critical for placental development and fetal growth in mammals. Aberrant epigenetic profiles at imprinted loci, such as DNA methylation defects, are surprisingly rare in pregnancies with compromised fetal growth, while variations in transcriptional output from the expressed alleles of imprinted genes are more commonly reported in pregnancies complicated with intrauterine growth restriction (IUGR). To determine if PLAGL1 and HYMAI, two imprinted transcripts deregulated in Transient Neonatal Diabetes Mellitus, are involved in non-syndromic IUGR we compared the expression and DNA methylation levels in a large cohort of placental biopsies from IUGR and uneventful pregnancies. This revealed that despite appropriate maternal methylation at the shared PLAGL1/HYMAI promoter, there was a loss of correlation between PLAGL1 and HYMAI expression in IUGR. This incongruity was due to higher HYMAI expression in IUGR gestations, coupled with PLAGL1 down-regulation in placentas from IUGR girls, but not boys. The PLAGL1 protein is a zinc-finger transcription factor that has been shown to be a master coordinator of a genetic growth network in mice. We observe PLAGL1 binding to the H19/IGF2 shared enhancers in placentae, with significant correlations between PLAGL1 levels with H19 and IGF2 expression levels. In addition, PLAGL1 binding and expression also correlate with expression levels of metabolic regulator genes SLC2A4, TCF4 and PPAR gamma 1. Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta.
publishDate 2014
dc.date.none.fl_str_mv 2014
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6554
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6554
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv OXFORD UNIV PRESS
publisher.none.fl_str_mv OXFORD UNIV PRESS
dc.source.none.fl_str_mv HUMAN MOLECULAR GENETICS
ISSN: 09646906
ISSNe: 14602083
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
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