PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived...

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Main Authors: Dagne Daskeviciute, Becky Sainty, Louise Chappell-Maor, Caitlin Bone, Sarah Russell, Isabel Iglesias-Platas, Philippe Arnaud, Ana Monteagudo-Sánchez, Maxim V.C Greenberg, Keran Chen, Africa Manero Azua, Guiomar Perez de Nanclares, Jon Lartey, David Monk
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Epigenetics
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Online Access:https://www.tandfonline.com/doi/10.1080/15592294.2025.2523191
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author Dagne Daskeviciute
Becky Sainty
Louise Chappell-Maor
Caitlin Bone
Sarah Russell
Isabel Iglesias-Platas
Philippe Arnaud
Ana Monteagudo-Sánchez
Maxim V.C Greenberg
Keran Chen
Africa Manero Azua
Guiomar Perez de Nanclares
Jon Lartey
David Monk
author_facet Dagne Daskeviciute
Becky Sainty
Louise Chappell-Maor
Caitlin Bone
Sarah Russell
Isabel Iglesias-Platas
Philippe Arnaud
Ana Monteagudo-Sánchez
Maxim V.C Greenberg
Keran Chen
Africa Manero Azua
Guiomar Perez de Nanclares
Jon Lartey
David Monk
author_sort Dagne Daskeviciute
collection DOAJ
description Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of bona fide imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, PIK3R1 and G0S2, both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.
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spelling doaj-art-39d6bb5048b740e69d3e050b7c6db1382025-08-20T03:15:59ZengTaylor & Francis GroupEpigenetics1559-22941559-23082025-12-0120110.1080/15592294.2025.2523191PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylationDagne Daskeviciute0Becky Sainty1Louise Chappell-Maor2Caitlin Bone3Sarah Russell4Isabel Iglesias-Platas5Philippe Arnaud6Ana Monteagudo-Sánchez7Maxim V.C Greenberg8Keran Chen9Africa Manero Azua10Guiomar Perez de Nanclares11Jon Lartey12David Monk13Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKNeonatology Department, BCNatal - Centre de Medicina Maternofetal i Neonatologia de Barcelona, Institut de Recerca Sant Joan de Déu, Barcelona, SpainInstitut Genetique, Reproduction and Developpement (GReD), CNRS- Universitié Clermont Auvergne-INSERM, Clermont-Ferrand, FranceUniversitè Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceUniversitè Paris Cité, CNRS, Institut Jacques Monod, Paris, FranceBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKRare Diseases Research Group, Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Araba University Hospital-Txagorritxu, Vitoria-Gasteiz, SpainRare Diseases Research Group, Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Araba University Hospital-Txagorritxu, Vitoria-Gasteiz, SpainDepartment of Obstetrics and Gynaecology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UKBiomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UKGenomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of bona fide imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, PIK3R1 and G0S2, both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.https://www.tandfonline.com/doi/10.1080/15592294.2025.2523191Genomic imprintingplacentadifferentially methylated regions
spellingShingle Dagne Daskeviciute
Becky Sainty
Louise Chappell-Maor
Caitlin Bone
Sarah Russell
Isabel Iglesias-Platas
Philippe Arnaud
Ana Monteagudo-Sánchez
Maxim V.C Greenberg
Keran Chen
Africa Manero Azua
Guiomar Perez de Nanclares
Jon Lartey
David Monk
PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
Epigenetics
Genomic imprinting
placenta
differentially methylated regions
title PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
title_full PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
title_fullStr PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
title_full_unstemmed PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
title_short PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
title_sort pik3r1 and g0s2 are human placenta specific imprinted genes associated with germline inherited maternal dna methylation
topic Genomic imprinting
placenta
differentially methylated regions
url https://www.tandfonline.com/doi/10.1080/15592294.2025.2523191
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