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

Ueda, Junji; Harada, Akihito; Urahama, Takashi; Machida, Shuichi; Maehara, Kazuhira; Hada, Masashi; Makino, Yoshinori; Nogami, Jumpei; Horikoshi, Naoki; Osakabe, Akihisa; Taguchi, Hiroyuki; Tanaka, H.; Tachiwana, Hiroaki; Yao, Tatsuma; Yamada, Minami; Iwamoto, Takashi; Isotani, Ayako; Ikawa, Masahito; Tachibana, Taro; Okada, Yuki; Kimurâ, Hiroshi; Ohkawa, Yasuyuki; Kurumizaka, Hitoshi; Yamagata, Kazuya

doi:10.1016/j.celrep.2016.12.065

Cited by 88 publications

(64 citation statements)

References 24 publications

(33 reference statements)

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“…This idea is supported by structural data showing that histone variants alter nucleosome properties (3,8–18). Some histone variants evolved only amongst specific taxa, such as testicular H3 in mammals (19,20), sperm specific variants in plants (21), H2A.W in land plants (22), macroH2A in metazoans (23), H2A.L and H2A.B in mammals (24) and sperm specific variants H2A.Q and H2A.R in mammals (25). …”

Section: Introductionmentioning

confidence: 99%

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Osakabe

Lorković

Kobayashi

et al. 2018

Nucleic Acids Research

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In eukaryotes, variants of core histone H2A are selectively incorporated in distinct functional domains of chromatin and are distinguished by conserved sequences of their C-terminal tail, the L1 loop and the docking domain, suggesting that each variant confers specific properties to the nucleosome. Chromatin of flowering plants contains four types of H2A variants, which biochemical properties have not been characterized. We report that in contrast with animals, in Arabidopsis thaliana H2A variants define only four major types of homotypic nucleosomes containing exclusively H2A, H2A.Z, H2A.X or H2A.W. In vitro assays show that the L1 loop and the docking domain confer distinct stability of the nucleosome. In vivo and in vitro assays suggest that the L1 loop and the docking domain cooperate with the C-terminal tail to regulate chromatin accessibility. Based on these findings we conclude that the type of H2A variant in the nucleosome impacts on its interaction with DNA and propose that H2A variants regulate the dynamics of chromatin accessibility. In plants, the predominance of homotypic nucleosomes with specific physical properties and their specific localization to distinct domains suggest that H2A variants play a dominant role in chromatin dynamics and function.

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Section: Introductionmentioning

confidence: 99%

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Osakabe

Lorković

Kobayashi

et al. 2018

Nucleic Acids Research

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“…H3t is synthesized in spermatogonia and remains detectable in spermatocytes and early spermatids (Trostle-Weige et al, 1984). Despite that the other H3 variants are localized in all stages of germ cell types, these two H3 variants are thought to be involved in cellular proliferation and development by opening the chromatin structure as we recently reported (Ueda et al, 2017).…”

Section: Introductionmentioning

confidence: 71%

“…4), indicating that decreased expression of H3.5 per se may be involved in the deterioration of cellular function. Recently, we showed that the function of H3t is essential for the initial step of spermatogenesis and is required for spermatogonia (i.e., spermatogenic stem cells) to enter differentiation (Ueda et al, 2017). Based on the microscopic appearance of the chromosomal material, the primary spermatocyte stage was subdivided into preleptotene, leptotene, zygonema, pachynema, diplonema, and diakinesis.…”

Section: Discussionmentioning

confidence: 99%

“…Among them, H3.5 is specifically expressed in the seminiferous tubules of human testes (Schenk et al, 2011), mainly in spermatogonia and primary spermatocytes (Urahama et al, 2016). Despite that the other H3 variants are localized in all stages of germ cell types, these two H3 variants are thought to be involved in cellular proliferation and development by opening the chromatin structure as we recently reported (Ueda et al, 2017). Despite that the other H3 variants are localized in all stages of germ cell types, these two H3 variants are thought to be involved in cellular proliferation and development by opening the chromatin structure as we recently reported (Ueda et al, 2017).…”

Section: Introductionmentioning

confidence: 88%

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Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders

et al. 2017

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Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin's solution-fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and PCNA expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene/leptotene-stage primary spermatocytes, especially during germinal stages VI-X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p < 0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p < 0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy. Different from other testis-specific histones, which are often expressed during the histone-to-protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.

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“…During spermatogonia differentiation, H3t replaces canonical H3 proteins, thus forming a more open chromatin structure. H3t (H3T) containing nucleosomes are required for spermatogonial differentiation, and ensure entry into meiosis, as H3t gene deficiency leads to male infertility due to the failure of germ cell differentiation from spermatogonia to spermatocytes (Ueda et al 2017). CENPA is another histone H3 variant that is specifically localized at the centromeres and modulates their behavior (Niikura et al 2015).…”

Section: Histone H3 Variants In Meiosismentioning

confidence: 99%

The histone codes for meiosis

Wang

Khawar

et al. 2017

Reproduction

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Meiosis is a specialized process that produces haploid gametes from diploid cells by a single round of DNA replication followed by two successive cell divisions. It contains many special events, such as programmed DNA double-strand break (DSB) formation, homologous recombination, crossover formation and resolution. These events are associated with dynamically regulated chromosomal structures, the dynamic transcriptional regulation and chromatin remodeling are mainly modulated by histone modifications, termed 'histone codes'. The purpose of this review is to summarize the histone codes that are required for meiosis during spermatogenesis and oogenesis, involving meiosis resumption, meiotic asymmetric division and other cellular processes. We not only systematically review the functional roles of histone codes in meiosis but also discuss future trends and perspectives in this field.Reproduction (2017) 154 R65-R79

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

Cited by 88 publications

References 24 publications

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Histone H2A variants confer specific properties to nucleosomes and impact on chromatin accessibility

Roles of histone H3.5 in human spermatogenesis and spermatogenic disorders

The histone codes for meiosis

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