PMID- 34619096 OWN - NLM STAT- MEDLINE DCOM- 20211215 LR - 20211215 IS - 1878-1551 (Electronic) IS - 1534-5807 (Linking) VI - 56 IP - 20 DP - 2021 Oct 25 TI - Analysis of developmental imprinting dynamics in primates using SNP-free methods to identify imprinting defects in cloned placenta. PG - 2826-2840.e7 LID - S1534-5807(21)00730-9 [pii] LID - 10.1016/j.devcel.2021.09.012 [doi] AB - Our knowledge of genomic imprinting in primates is lagging behind that of mice largely because of the difficulties of allelic analyses in outbred animals. To understand imprinting dynamics in primates, we profiled transcriptomes, DNA methylomes, and H3K27me3 in uniparental monkey embryos. We further developed single-nucleotide-polymorphism (SNP)-free methods, TARSII and CARSII, to identify germline differentially methylated regions (DMRs) in somatic tissues. Our comprehensive analyses showed that allelic DNA methylation, but not H3K27me3, is a major mark that correlates with paternal-biasedly expressed genes (PEGs) in uniparental monkey embryos. Interestingly, primate germline DMRs are different from PEG-associated DMRs in early embryos and are enriched in placenta. Strikingly, most placenta-specific germline DMRs are lost in placenta of cloned monkeys. Collectively, our study establishes SNP-free germline DMR identification methods, defines developmental imprinting dynamics in primates, and demonstrates imprinting defects in cloned monkey placenta, which provides important clues for improving primate cloning. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Chu, Chu AU - Chu C AD - State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. FAU - Zhang, Wenhao AU - Zhang W AD - Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: wenhao.zhang@childrens.harvard.edu. FAU - Kang, Yu AU - Kang Y AD - State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. FAU - Si, Chenyang AU - Si C AD - State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. FAU - Ji, Weizhi AU - Ji W AD - State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China. Electronic address: wji@lpbr.cn. FAU - Niu, Yuyu AU - Niu Y AD - State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China; Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: niuyy@lpbr.cn. FAU - Zhang, Yi AU - Zhang Y AD - Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Division of Hematology/Oncology, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, WAB-149G, 200 Longwood Avenue, Boston, MA 02115, USA. Electronic address: yzhang@genetics.med.harvard.edu. LA - eng GR - HHMI/Howard Hughes Medical Institute/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211006 PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 SB - IM MH - Alleles MH - Animals MH - DNA Methylation/*physiology MH - Embryo, Mammalian/*metabolism MH - Female MH - Genomic Imprinting/*genetics MH - Germ Cells MH - Placenta/*metabolism MH - Pregnancy MH - Primates OTO - NOTNLM OT - CARSII OT - SCNT OT - SNP free OT - TARSII OT - cloning OT - germline DMR OT - imprint OT - imprinting dynamics OT - monkey OT - primates COIS- Declaration of interests The authors declare no competing interests. EDAT- 2021/10/08 06:00 MHDA- 2021/12/16 06:00 CRDT- 2021/10/07 20:14 PHST- 2021/06/12 00:00 [received] PHST- 2021/08/25 00:00 [revised] PHST- 2021/09/10 00:00 [accepted] PHST- 2021/10/08 06:00 [pubmed] PHST- 2021/12/16 06:00 [medline] PHST- 2021/10/07 20:14 [entrez] AID - S1534-5807(21)00730-9 [pii] AID - 10.1016/j.devcel.2021.09.012 [doi] PST - ppublish SO - Dev Cell. 2021 Oct 25;56(20):2826-2840.e7. doi: 10.1016/j.devcel.2021.09.012. Epub 2021 Oct 6.