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Monk D.,Imprinting and Cancer Group
Briefings in Functional Genomics and Proteomics | Year: 2010

Genetic events alone cannot explain the entire process of carcinogenesis. It is estimated that there are more epigenetic alterations in cancer than DNA mutations, and disiphering driver and secondary events is essential to understand early processes of tumorigenesis. Epigenetic modifications control gene activity, governing whether a gene is transcribed or silent. In cancer, global patterns of two epigenetic marks, histone modifications and DNA methylation, are known to be extensively deregulated. Tumour cells are also characterized by loss-of-imprinting, a key epigenetic developmental mechanism. Genomic imprinting is the parent-of-origin, monoallelic expression of genes and is controlled by differentially DNA-methylated regions and allelic-histone modifications. With specific emphasis on imprinted loci this review will discuss alterations in DNA methylation and histone modifications in cancer. The recent advances in technology that might facilitate the identification and characterization of the epigenetic profiles of cancer will also be described. © The Author 2010. Published by Oxford University Press. All rights reserved.


Iglesias-Platas I.,Hospital Sant Joan Of Deu | Martin-Trujillo A.,Imprinting and Cancer Group | Petazzi P.,Hospital Duran i Reynals | Guillaumet-Adkins A.,Hospital Sant Joan Of Deu | And 4 more authors.
Human molecular genetics | Year: 2014

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 PPARγ1. Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


PubMed | Hospital Sant Joan Of Deu, Hospital Duran i Reynals, Imprinting and Cancer Group and University of Barcelona
Type: Journal Article | Journal: Human molecular genetics | Year: 2014

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 PPAR1. Our results strongly suggest that fetal growth can be influenced by altered expression of the PLAGL1 gene network in human placenta.

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