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ToolsDaskeviciute, Dagne, Chappell-Maor, Louise, Sainty, Becky, Arnaud, Philippe, Iglesias-Platas, Isabel, Simon, Carlos, Okae, Hiroaki, Arima, Takahiro, Vassena, Rita, Lartey, Jon and Monk, David (2025) Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans. Human Molecular Genetics, 34 (7). pp. 626-638. ISSN 0964-6906
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Abstract
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.
| Item Type: | Article |
|---|---|
| Additional Information: | This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO BFU2017-85571-R to D.M.), co-funded with the European Union Regional Development Fund (FEDER); the Medical Research Council (MR/T032863/1 to D.M.); the National Institute for Health and Care Research (NIHR) Capability Fund; the UKRI Biotechnology and Biological Sciences Research Council (BB/V016156/1 to D.M.); R.S. and D.D. received BBSRC Norwich Research Park Biosciences Doctoral Training Partnership fellowships (BB/T008717/1). |
| Uncontrolled Keywords: | dna methylation,imprinting,placenta,pre-implantation embryos,molecular biology,genetics,genetics(clinical) ,/dk/atira/pure/subjectarea/asjc/1300/1312 |
| 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: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Apr 2025 13:30 |
| Last Modified: | 02 May 2025 00:18 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99133 |
| DOI: | 10.1093/hmg/ddaf009 |
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