Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Jun Ueda; Akihito Harada; Takashi Urahama; Shinichi Machida; Kazumitsu Maehara; Masashi Hada; Yoshinori Makino; Jumpei Nogami; Naoki Horikoshi; Akihisa Osakabe; Hiroyuki Taguchi; Hiroki Tanaka; Hiroaki Tachiwana; Tatsuma Yao; Minami Yamada; Takashi Iwamoto; Ayako Isotani; Masahito Ikawa; Taro Tachibana; Yuki Okada; Hiroshi Kimura; Yasuyuki Ohkawa; Hitoshi Kurumizaka; Kazuo Yamagata

doi:10.1016/j.celrep.2016.12.065

Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Jun Ueda^*, Akihito Harada, Takashi Urahama, Shinichi Machida, Kazumitsu Maehara, Masashi Hada, Yoshinori Makino, Jumpei Nogami, Naoki Horikoshi, Akihisa Osakabe, Hiroyuki Taguchi, Hiroki Tanaka, Hiroaki Tachiwana, Tatsuma Yao, Minami Yamada, Takashi Iwamoto, Ayako Isotani, Masahito Ikawa, Taro Tachibana, Yuki OkadaHiroshi Kimura, Yasuyuki Ohkawa, Hitoshi Kurumizaka, Kazuo Yamagata

^*Corresponding author for this work

Waseda Research Institute for Science and Engineering

Research output: Contribution to journal › Article › peer-review

57 Citations (Scopus)

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.

Original language	English
Pages (from-to)	593-600
Number of pages	8
Journal	Cell Reports
Volume	18
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2016.12.065
Publication status	Published - 2017 Jan 17

Keywords

chromatin
crystal structure
epigenetics
histone variant
meiosis
nucleosome
spermatogenesis
spermatogonial differentiation
spermatozoa
testes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2016.12.065

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Ueda, J., Harada, A., Urahama, T., Machida, S., Maehara, K., Hada, M., Makino, Y., Nogami, J., Horikoshi, N., Osakabe, A., Taguchi, H., Tanaka, H., Tachiwana, H., Yao, T., Yamada, M., Iwamoto, T., Isotani, A., Ikawa, M., Tachibana, T., ... Yamagata, K. (2017). Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis. Cell Reports, 18(3), 593-600. https://doi.org/10.1016/j.celrep.2016.12.065

Ueda, J, Harada, A, Urahama, T, Machida, S, Maehara, K, Hada, M, Makino, Y, Nogami, J, Horikoshi, N, Osakabe, A, Taguchi, H, Tanaka, H, Tachiwana, H, Yao, T, Yamada, M, Iwamoto, T, Isotani, A, Ikawa, M, Tachibana, T, Okada, Y, Kimura, H, Ohkawa, Y, Kurumizaka, H & Yamagata, K 2017, 'Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis', Cell Reports, vol. 18, no. 3, pp. 593-600. https://doi.org/10.1016/j.celrep.2016.12.065

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AU - Ueda, Jun

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AU - Maehara, Kazumitsu

AU - Hada, Masashi

AU - Makino, Yoshinori

AU - Nogami, Jumpei

AU - Horikoshi, Naoki

AU - Osakabe, Akihisa

AU - Taguchi, Hiroyuki

AU - Tanaka, Hiroki

AU - Tachiwana, Hiroaki

AU - Yao, Tatsuma

AU - Yamada, Minami

AU - Iwamoto, Takashi

AU - Isotani, Ayako

AU - Ikawa, Masahito

AU - Tachibana, Taro

AU - Okada, Yuki

AU - Kimura, Hiroshi

AU - Ohkawa, Yasuyuki

AU - Kurumizaka, Hitoshi

AU - Yamagata, Kazuo

PY - 2017/1/17

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N2 - 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.

AB - 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.

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KW - epigenetics

KW - histone variant

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KW - testes

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Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Abstract

Keywords

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