title: Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis.
abstract: Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.
authors.affiliation: Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi 487-8501, Japan; Center for Genetic Analysis of Biological Responses, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan. Electronic address: junueda@isc.chubu.ac.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Ueda
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Harada
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Urahama
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Machida
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Maehara
authors.affiliation: Laboratory of Pathology and Development, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hada
authors.affiliation: Laboratory of Pathology and Development, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Makino
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Nogami
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Horikoshi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Osakabe
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Taguchi
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tachiwana
authors.affiliation: Research and Development Center, Fuso Pharmaceutical Industries, Ltd., Osaka 536-8523, Japan; Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama 649-6493, Japan.
authors.forename: Tatsuma
authors.initials: T
authors.lastname: Yao
authors.affiliation: Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Center for Education in Laboratory Animal Research, Chubu University, Kasugai, Aichi 487-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Center for Genetic Analysis of Biological Responses, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Isotani
authors.affiliation: Center for Genetic Analysis of Biological Responses, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, Osaka City University, Osaka 558-8585, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Tachibana
authors.affiliation: Laboratory of Pathology and Development, Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113-0032, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohkawa
authors.affiliation: Laboratory of Structural Biology, Graduate School of Advanced Science & Engineering, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurumizaka
authors.affiliation: Center for Genetic Analysis of Biological Responses, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan; Faculty of Biology-Oriented Science and Technology, Kindai University, Kinokawa, Wakayama 649-6493, Japan. Electronic address: yamagata@waka.kindai.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053713:Azoospermia / Q000209:etiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006238:Haploidy; D006657:Histones / Q000737:chemistry / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D013091:Spermatogenesis; D013093:Spermatogonia / Q000378:metabolism*; D013737:Testis / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; C507675:REC8 protein, human; C102019:Stra8 protein, mouse
keywords: chromatin; crystal structure; epigenetics; histone variant; meiosis; nucleosome; spermatogenesis; spermatogonial differentiation; spermatozoa; testes