Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans
Por:
Daskeviciute D, Chappell-Maor L, Sainty B, Arnaud P, Iglesias-Platas I, Simon C, Okae H, Arima T, Vassena R, Lartey J and Monk D
Publicada:
17 ene 2025
Ahead of Print:
1 ene 2025
Resumen:
Genomic imprinting is the parent-of-origin dependent monoallelic expression of genes often associated with regions of germline-derived DNA methylation that are maintained as differentially methylated regions (gDMRs) in somatic tissues. This form of epigenetic regulation is highly conserved in mammals and is thought to have co-evolved with placentation. Tissue-specific gDMRs have been identified in human placenta, suggesting that species-specific imprinting dependent on unorthodox epigenetic establishment or maintenance may be more widespread than previously anticipated. Non-canonical imprinting, reliant on differential allelic H3K27me3 enrichment, has been reported in mouse and rat pre-implantation embryos, often overlapping long terminal repeat (LTR)-derived promoters. These non-canonical imprints lose parental allele-specific H3K27me3 specificity, subsequently gaining DNA methylation on the same allele in extra-embryonic tissues resulting in placenta-specific, somatically acquired maternal DMRs. To determine if similar non-canonical imprinting is present in the human placenta, we interrogated allelic DNA methylation for a selected number of loci, including (i) the human orthologues of non-canonical imprinted regions in mouse and rat, (ii) promoters of human LTR-derived transcripts, and (iii) CpG islands with intermediate placenta-specific methylation that are unmethylated in gametes and pre-implantation embryos. We failed to identify any non-canonical imprints in the human placenta whole villi samples. Furthermore, the assayed genes were shown to be biallelically expressed in human pre-implantation embryos, indicating they are not imprinted at earlier time points. Together, our work reiterates the continued evolution of placenta-specific imprinting in mammals, which we suggest is linked to epigenetic differences during the maternal-to-embryo transition and species-specific integration of retrotransposable elements.
Filiaciones:
Daskeviciute D:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park, Earlham Road, Norwich NR4 6PN, United Kingdom
Chappell-Maor L:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park, Earlham Road, Norwich NR4 6PN, United Kingdom
Sainty B:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park, Earlham Road, Norwich NR4 6PN, United Kingdom
Arnaud P:
Université Clermont Auvergne, CNRS, Inserm, GReD, 49 bd François Mitterrand, Clermont-Ferrand 63001, France
Iglesias-Platas I:
Institut de Recerca, Sant Joan de Déu, C. de Sta. Rosa, 39, Barcelona 08950, Spain
Neonatal Research, Norwich and Norwich University Hospital NHS Foundation Trust, Colney Ln, Norwich NR4 7UY, United Kingdom
Simon C:
Carlos Simon Foundation, Rda. de Narcís Monturiol, 11, Bloque C, 46980 Paterna, Valencia, Spain
Department of Obstetrics and Gynecology, Valencia University and INCLIVA, Av. Blasco Ibáñez 15, Valencia 46012, Spain
Okae H:
Department of Trophoblast Research, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan
Arima T:
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Vassena R:
Fecundis, C/Baldoro i Reixac 10-12, Barcelona 08028, Spain
Lartey J:
Department of Obstetrics and Gynaecology, Norwich and Norwich University Hospital NHS Foundation Trust, Colney Ln, Norwich NR4 7UY, United Kingdom
Monk D:
Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park, Earlham Road, Norwich NR4 6PN, United Kingdom
Bellvitge Biomedical Research Institute, Avinguda de la Granvia de l'Hospitalet 199, L'Hospitalet de Llobregat, Barcelona 08908, Spain
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