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

Daskeviciute, Dagne, Sainty, Becky, Chappell-Maor, Louise, Bone, Caitlin, Russell, Sarah, Iglesias-Platas, Isabel, Arnaud, Philippe, Monteagudo-Sánchez, Ana, Greenberg, Maxim V. C., Chen, Keran, Manerao-Azua, Africa, Perez de Nanclares, Guiomar, Lartey, Jon and Monk, David (2025) PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. Epigenetics, 20 (1). ISSN 1559-2294

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Abstract

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.

Item Type:	Article
Additional Information:	Data availability statement: The molecular data that support the findings of this study are available from the corresponding author [DM], upon reasonable request. However, patients did not consent to share meta-data. Funding: This work was supported by the Spanish Ministry of Economy and Competitiveness under grant [BFU2014–53093-R] and [BFU2017–85571-R], co-funded with the European Union Regional Development Fund (FEDER); UK Biotechnology and Biological Sciences Research Council under grant [BB/V016156/1]; Medical Research Council under grant [MR/T032863/1]. AMS was a recipient of an FPI PhD studentship from MINECO [BES-2015-072547], as well as FRM [SPF202004011789] and Fondation ARC [ARCPD12020070002563] postdoctoral fellowships, while DD, BS and KC are recipients of BBSRC Doctoral Training Partnership PhD fellowships. The human embryonic and fetal material was provided by the Joint MRC/Wellcome Trust [Grant # MR/006237/1] Human Developmental Biology Resource (http://www.hdbr.org).
Faculty \ School:	Faculty of Science > School of Biological Sciences Faculty of Science > The Sainsbury Laboratory Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	https://www.tandfonline.com/doi/full/10....
Depositing User:	LivePure Connector
Date Deposited:	30 Jun 2025 11:30
Last Modified:	30 Jun 2025 11:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99771
DOI:	10.1080/15592294.2025.2523191

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