Human Oocyte-Derived Methylation Differences Persist in the Placenta Revealing Widespread Transient Imprinting.
Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs) associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation.
Imprinting and Cancer group, Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain.
Marta
http://orcid.org/0000-0002-1412-9011
M
Sanchez-Delgado
Laboratoire GReD, CNRS, UMR6293, Clermont-Ferrand, France.
Franck
F
Court
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain.
Enrique
http://orcid.org/0000-0002-4217-1807
E
Vidal
Fundación IVI-Instituto Universitario IVI- INCLIVA, Department of Obs/Gyn, Valenica University, Valencia, Spain.
Jose
http://orcid.org/0000-0002-7616-1375
J
Medrano
Imprinting and Cancer group, Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain.
Ana
http://orcid.org/0000-0002-1432-1185
A
Monteagudo-Sánchez
Imprinting and Cancer group, Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain.
Alex
A
Martin-Trujillo
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
Chiharu
C
Tayama
Neonatal service, Hospital Sant Joan de Déu, BCNatal Hospital Sant Joan de Déu i Clínic, Universitat de Barcelona, Barcelona, Spain.
Isabel
http://orcid.org/0000-0003-1960-7614
I
Iglesias-Platas
Biomedical Primate Research Center (BPRC), Rijswijk, The Netherlands.
Ivanela
I
Kondova
Biomedical Primate Research Center (BPRC), Rijswijk, The Netherlands.
Ronald
R
Bontrop
Fundación IVI-Instituto Universitario IVI- INCLIVA, Department of Obs/Gyn, Valenica University, Valencia, Spain.
Maria Eugenia
ME
Poo-Llanillo
Institute of Evolutionary Biology (UPF-CSIC), PRBB, Barcelona, Spain.|Catalan Institute of Research and Advanced Studies, (ICREA), Passeig de Lluís Companys, Barcelona, Spain.|Centro Nacional de Analisis Genomico (CRG-CNAG), Barcelona, Spain.
Tomas
http://orcid.org/0000-0002-5597-3075
T
Marques-Bonet
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.
Kazuhiko
K
Nakabayashi
Fundación IVI-Instituto Universitario IVI- INCLIVA, Department of Obs/Gyn, Valenica University, Valencia, Spain.
Carlos
C
Simón
Imprinting and Cancer group, Cancer Epigenetic and Biology Program, Institut d'Investigació Biomedica de Bellvitge, Hospital Duran i Reynals, Barcelona, Spain.
David
D
Monk
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D018392:Genomic Imprinting / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011323:Primates / Q000235:genetics / Q000254:growth & development; D013094:Spermatozoa / Q000378:metabolism