PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation
Por:
Daskeviciute D, Sainty B, Chappell-Maor L, Bone C, Russell S, Iglesias-Platas I, Arnaud P, Monteagudo-Sánchez A, Greenberg MVC, Chen K, Manerao-Azua A, Perez de Nanclares G, Lartey J and Monk D
Publicada:
31 dic 2025
Ahead of Print:
26 jun 2025
Resumen:
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.
Filiaciones:
Daskeviciute D:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Sainty B:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Chappell-Maor L:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Bone C:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Russell S:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Iglesias-Platas I:
Neonatology Department, BCNatal - Centre de Medicina Maternofetal i Neonatologia de Barcelona, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
Neonatal Intensive Care Unit, Norfolk Clinical Research Facility, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK
Arnaud P:
Institut Genetique, Reproduction and Developpement (GReD), CNRS- Universitié Clermont Auvergne-INSERM, Clermont-Ferrand, France
Monteagudo-Sánchez A:
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France
Greenberg MVC:
Université Paris Cité, CNRS, Institut Jacques Monod, Paris, France
Chen K:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Manerao-Azua A:
Rare Diseases Research Group, Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Araba University Hospital-Txagorritxu, Vitoria-Gasteiz, Spain
Perez de Nanclares G:
Rare Diseases Research Group, Molecular (Epi)Genetics Laboratory, Bioaraba Health Research Institute, Araba University Hospital-Txagorritxu, Vitoria-Gasteiz, Spain
Lartey J:
Department of Obstetrics and Gynaecology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK
Monk D:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich, UK
Green Submitted, Green Accepted, gold
|