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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.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf009","type":"journal-article","created":{"date-parts":[[2025,1,18]],"date-time":"2025-01-18T05:47:53Z","timestamp":1737179273000},"page":"626-638","source":"Crossref","is-referenced-by-count":10,"title":["Non-canonical imprinting, manifesting as post-fertilization placenta-specific parent-of-origin dependent methylation, is not conserved in humans"],"prefix":"10.1093","volume":"34","author":[{"given":"Dagne","family":"Daskeviciute","sequence":"first","affiliation":[{"name":"Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park , Earlham Road, Norwich NR4 6PN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Chappell-Maor","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park , Earlham Road, Norwich NR4 6PN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Becky","family":"Sainty","sequence":"additional","affiliation":[{"name":"Biomedical Research Centre, School of Biological Sciences, University of East Anglia, Norwich Research Park , Earlham Road, Norwich NR4 6PN ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-8764","authenticated-orcid":false,"given":"Philippe","family":"Arnaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, CNRS, Inserm, GReD , 49 bd Fran\u00e7ois Mitterrand, Clermont-Ferrand 63001 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Iglesias-Platas","sequence":"additional","affiliation":[{"name":"Institut de Recerca, Sant Joan de D\u00e9u , C. de Sta. Rosa, 39, Barcelona 08950 ,","place":["Spain"]},{"name":"Neonatal Research, Norwich and Norwich University Hospital NHS Foundation Trust , Colney Ln, Norwich NR4 7UY ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Simon","sequence":"additional","affiliation":[{"name":"Carlos Simon Foundation , Rda. de Narc\u00eds Monturiol, 11, Bloque C, 46980 Paterna, Valencia,","place":["Spain"]},{"name":"Department of Obstetrics and Gynecology, Valencia University and INCLIVA , Av. Blasco Ib\u00e1\u00f1ez 15, Valencia 46012 ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Okae","sequence":"additional","affiliation":[{"name":"Department of Trophoblast Research, Institute of Molecular Embryology and Genetics, Kumamoto University , Kumamoto 860-0811 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Arima","sequence":"additional","affiliation":[{"name":"Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine , Sendai 980-8575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Vassena","sequence":"additional","affiliation":[{"name":"Fecundis , C\/Baldoro i Reixac 10-12, Barcelona 08028 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