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Title: Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction
Author: Monteagudo Sánchez, Ana
Sánchez Delgado, Marta
Hernandez Mora, Jose Ramon
Tubío Santamaría, Nuria
Gratacós Solsona, Eduard
Esteller, Manel
López de Heredia, Miguel
Nunes Martínez, Virginia
Choux, Cecile
Fauque, Patricia
Perez de Nanclares, Guiomar
Anton, Lauren
Elovitz, Michal A.
Iglesias Platas, Isabel
Monk, David
Keywords: ADN
Retard del creixement intrauterí
Expressió gènica
Fetal growth retardation
Gene expression
Issue Date: 26-Feb-2019
Publisher: BioMed Central
Abstract: Background: genome-wide studies have begun to link subtle variations in both allelic DNA methylation and parent-of-origin genetic effects with early development. Numerous reports have highlighted that the placenta plays a critical role in coordinating fetal growth, with many key functions regulated by genomic imprinting. With the recent description of wide-spread polymorphic placenta-specific imprinting, the molecular mechanisms leading to this curious polymorphic epigenetic phenomenon is unknown, as is their involvement in pregnancies complications. Results: profiling of 35 ubiquitous and 112 placenta-specific imprinted differentially methylated regions (DMRs) using high-density methylation arrays and pyrosequencing revealed isolated aberrant methylation at ubiquitous DMRs as well as abundant hypomethylation at placenta-specific DMRs. Analysis of the underlying chromatin state revealed that the polymorphic nature is not only evident at the level of allelic methylation, but DMRs can also adopt an unusual epigenetic signature where the underlying histones are biallelically enrichment of H3K4 methylation, a modification normally mutually exclusive with DNA methylation. Quantitative expression analysis in placenta identified two genes, GPR1-AS1 and ZDBF2, that were differentially expressed between IUGRs and control samples after adjusting for clinical factors, revealing coordinated deregulation at the chromosome 2q33 imprinted locus. Conclusions: DNA methylation is less stable at placenta-specific imprinted DMRs compared to ubiquitous DMRs and contributes to privileged state of the placenta epigenome. IUGR-associated expression differences were identified for several imprinted transcripts independent of allelic methylation. Further work is required to determine if these differences are the cause IUGR or reflect unique adaption by the placenta to developmental stresses.
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It is part of: Clinical Epigenetics, 2019, vol. 11, num. 1, p. 35
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ISSN: 1868-7075
Appears in Collections:Articles publicats en revistes (BCNatal Fetal Medicine Research Center)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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