title: Paternal heterochromatin formation in human embryos is H3K9/HP1 directed and primed by sperm-derived histone modifications.
abstract: The different configurations of maternal and paternal chromatin, acquired during oogenesis and spermatogenesis, have to be rearranged after fertilization to form a functional embryonic genome. In the paternal genome, nucleosomal chromatin domains are re-established after the protamine-to-histone exchange. We investigated the formation of constitutive heterochromatin (cHC) in human preimplantation embryos. Our results show that histones carrying canonical cHC modifications are retained in cHC regions of sperm chromatin. These modified histones are transmitted to the oocyte and contribute to the formation of paternal embryonic cHC. Subsequently, the modifications are recognized by the H3K9/HP1 pathway maternal chromatin modifiers and propagated over the embryonic cleavage divisions. These results are in contrast to what has been described for mouse embryos, in which paternal cHC lacks canonical modifications and is initially established by Polycomb group proteins. Our results show intergenerational epigenetic inheritance of the cHC structure in human embryos.
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Christine
authors.initials: C
authors.lastname: van de Werken
authors.affiliation: 1] Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands [2] Department of Reproduction and Development, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Godfried W
authors.initials: GW
authors.lastname: van der Heijden
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Cindy
authors.initials: C
authors.lastname: Eleveld
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Teeuwssen
authors.affiliation: Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
authors.forename: Mareike
authors.initials: M
authors.lastname: Albert
authors.affiliation: Department of Reproduction and Development, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Willy M
authors.initials: WM
authors.lastname: Baarends
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.affiliation: 1] Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland [2] Faculty of Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel, Switzerland.
authors.forename: Antoine H F M
authors.initials: AH
authors.lastname: Peters
authors.affiliation: Division of Reproductive Medicine, Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Postbus 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Esther B
authors.initials: EB
authors.lastname: Baart
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D051379:Mice; D009865:Oocytes / Q000378:metabolism / Q000648:ultrastructure; D009866:Oogenesis / Q000235:genetics; D063146:Polycomb-Group Proteins / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism* / Q000648:ultrastructure; D015053:Zygote / Q000737:chemistry / Q000166:cytology / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D063146:Polycomb-Group Proteins; D000090266:Chromobox Protein Homolog 5