title: Long-Term Retention of CENP-A Nucleosomes in Mammalian Oocytes Underpins Transgenerational Inheritance of Centromere Identity.
abstract: Centromeres control genetic inheritance by directing chromosome segregation but are not genetically encoded themselves. Rather, centromeres are defined by nucleosomes containing CENP-A, a histone H3 variant [1]. In cycling somatic cells, centromere identity is maintained by an established cell-cycle-coupled CENP-A chromatin assembly pathway, but how centromeres are inherited through the mammalian female germline is unclear because of the long (months to decades) prophase I arrest. Here we show that mouse oocytes retain the pool of CENP-A nucleosomes assembled before birth, and that this pool is sufficient for centromere function, fertility, and genome transmission to embryos. Indeed, oocytes lack any measurable CENP-A nucleosome assembly through the entire fertile lifespan of the female (>1 year). Thus, the remarkable stability of CENP-A nucleosomes confers transgenerational centromere identity in mammals.
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Evan M
authors.initials: EM
authors.lastname: Smoak
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: lampson@sas.upenn.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Lampson
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: blackbe@mail.med.upenn.edu.
authors.forename: Ben E
authors.initials: BE
authors.lastname: Black
mesh_terms: D000818:Animals; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D009707:Nucleosomes / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*
chemical_list: D000076247:Centromere Protein A; D009707:Nucleosomes