title: Hira-mediated H3.3 incorporation is required for DNA replication and ribosomal RNA transcription in the mouse zygote.
abstract: Extensive chromatin reprogramming occurs at fertilization and is thought to be under the control of maternal factors, but the underlying mechanisms remain poorly understood. We report that maternal Hira, a chaperone for the histone variant H3.3, is required for mouse development past the zygote stage. Male pronucleus formation is inhibited upon deletion of Hira due to a lack of nucleosome assembly in the sperm genome. Hira mutant oocytes are incapable of developing parthenogenetically, indicative of a role for Hira in the female genome. Both parental genomes show highly reduced levels of DNA replication and transcription in the mutants. It has long been thought that transcription is not required for zygote development. Surprisingly, we found that Hira/H3.3-dependent transcription of ribosomal RNA is required for first cleavage. Our results demonstrate that Hira-mediated H3.3 incorporation is essential for parental genome reprogramming and reveal an unexpected role for rRNA transcription in the mouse zygote.
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Fong Ming
authors.initials: FM
authors.lastname: Koh
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Wong
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Conti
authors.affiliation: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA. Electronic address: miguel.ramalho-santos@ucsf.edu.
authors.forename: Miguel
authors.initials: M
authors.lastname: Ramalho-Santos
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D004261:DNA Replication / Q000235:genetics* / Q000502:physiology; D005306:Fertilization / Q000235:genetics / Q000502:physiology; D056488:Histone Chaperones / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012335:RNA, Ribosomal / Q000378:metabolism*; D013094:Spermatozoa / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015053:Zygote / Q000254:growth & development / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; C484187:Hira protein, mouse; D056488:Histone Chaperones; D006657:Histones; D012335:RNA, Ribosomal; D014157:Transcription Factors
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