Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction
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 re...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-019-0630-4 |
| _version_ | 1828475583244271616 |
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| author | Ana Monteagudo-Sánchez Marta Sánchez-Delgado Jose Ramon Hernandez Mora Nuria Tubío Santamaría Eduard Gratacós Manel Esteller Miguel López de Heredia Virgina Nunes Cecile Choux Patricia Fauque Guiomar Perez de Nanclares Lauren Anton Michal A. Elovitz Isabel Iglesias-Platas David Monk |
| author_facet | Ana Monteagudo-Sánchez Marta Sánchez-Delgado Jose Ramon Hernandez Mora Nuria Tubío Santamaría Eduard Gratacós Manel Esteller Miguel López de Heredia Virgina Nunes Cecile Choux Patricia Fauque Guiomar Perez de Nanclares Lauren Anton Michal A. Elovitz Isabel Iglesias-Platas David Monk |
| author_sort | Ana Monteagudo-Sánchez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:16:40Z |
| format | Article |
| id | doaj.art-9d5ca46d9ac84d09bb6127d3c0d24f71 |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-11T06:16:40Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-9d5ca46d9ac84d09bb6127d3c0d24f712022-12-22T01:17:58ZengBMCClinical Epigenetics1868-70751868-70832019-02-0111111510.1186/s13148-019-0630-4Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restrictionAna Monteagudo-Sánchez0Marta Sánchez-Delgado1Jose Ramon Hernandez Mora2Nuria Tubío Santamaría3Eduard Gratacós4Manel Esteller5Miguel López de Heredia6Virgina Nunes7Cecile Choux8Patricia Fauque9Guiomar Perez de Nanclares10Lauren Anton11Michal A. Elovitz12Isabel Iglesias-Platas13David Monk14Imprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLImprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLImprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLImprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLFetal I+D Fetal Medicine Research Center, BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Clínic and Hospital Sant Joan de DéuCancer Epigenetics group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLHuman Molecular Genetics group, Genes, disease and Therapy Program, Bellvitge Biomedical Research Institute - IDIBELL, Av. Gran Via de L’Hospitalet 199-203Department of Physiological Sciences II, School of Medicine, University of BarcelonaUniversité Bourgogne Franche-Comté - INSERM UMR1231Université Bourgogne Franche-Comté - INSERM UMR1231(Epi) Genetics Laboratory, BioAraba National Health Institute, Hospital Universitario Araba-TxagorritxuMaternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, University of PennsylvaniaMaternal and Child Health Research Program, Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, University of PennsylvaniaGReN (Grup de Reçerca en Neonatologia), BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine, Institut de Reçerca Sant Joan de DéuImprinting and Cancer Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute – IDIBELLAbstract 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.http://link.springer.com/article/10.1186/s13148-019-0630-4ImprintingPlacentaDNA methylationEpigenetics |
| spellingShingle | Ana Monteagudo-Sánchez Marta Sánchez-Delgado Jose Ramon Hernandez Mora Nuria Tubío Santamaría Eduard Gratacós Manel Esteller Miguel López de Heredia Virgina Nunes Cecile Choux Patricia Fauque Guiomar Perez de Nanclares Lauren Anton Michal A. Elovitz Isabel Iglesias-Platas David Monk Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction Clinical Epigenetics Imprinting Placenta DNA methylation Epigenetics |
| title | Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction |
| title_full | Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction |
| title_fullStr | Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction |
| title_full_unstemmed | Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction |
| title_short | Differences in expression rather than methylation at placenta-specific imprinted loci is associated with intrauterine growth restriction |
| title_sort | differences in expression rather than methylation at placenta specific imprinted loci is associated with intrauterine growth restriction |
| topic | Imprinting Placenta DNA methylation Epigenetics |
| url | http://link.springer.com/article/10.1186/s13148-019-0630-4 |
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