Disruption of Th2a and Th2b genes causes defects in spermatogenesis.
The variant histones TH2A and TH2B are abundant in the testis, but their roles in spermatogenesis remain elusive. Here, we show that male mutant mice lacking both Th2a and Th2b genes were sterile, with few sperm in the epididymis. In the mutant testis, the lack of TH2B was compensated for by overexpression of H2B, whereas overexpression of H2A was not observed, indicating a decrease in the total histone level. Mutant mice exhibited two defects: incomplete release of cohesin at interkinesis after meiosis I and histone replacement during spermiogenesis. In the mutant testis, secondary spermatocytes at interkinesis accumulated and cohesin was not released normally, suggesting that the retained cohesion of sister chromatids delayed the subsequent entry into meiosis II. In addition, impaired chromatin incorporation of TNP2 and degenerated spermatids were observed in the mutant testis. These results suggest that a loss of TH2A and TH2B function in chromatin dynamics or a decrease in the total histone levels causes defects in both cohesin release and histone replacement during spermatogenesis.
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan sinagawa@rtc.riken.jp sishii@rtc.riken.jp.
Toshie
T
Shinagawa
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Linh My
LM
Huynh
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Tsuyoshi
T
Takagi
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Daisuke
D
Tsukamoto
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Chinatsu
C
Tomaru
Global Research Cluster, RIKEN, Graduate School of Science and Engineering, Saitama University, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Ho-Geun
HG
Kwak
Global Research Cluster, RIKEN, Graduate School of Science and Engineering, Saitama University, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
Naoshi
N
Dohmae
Division of Animal Sciences, National Institute of Agrobiological Sciences, 2-1-2 Kannondai, Tsukuba, Ibaraki 305-0856, Japan.
Junko
J
Noguchi
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan CREST Research Project of JST (Japan Science and Technology Agency), 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan sinagawa@rtc.riken.jp sishii@rtc.riken.jp.
Shunsuke
S
Ishii
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D033481:Chromosomes, Mammalian / Q000378:metabolism; D004268:DNA-Binding Proteins; D005260:Female; D017353:Gene Deletion; D006657:Histones / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008540:Meiosis; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D000097722:Cohesins
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D000097722:Cohesins; C489505:Tnp2 protein, mouse; C081018:histone H2B type 1-A
Cohesin; Histone replacement; Histone variants; Mouse; Spermatogenesis