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

Publication date: 17 January 2017
Source:Cell Reports, Volume 18, Issue 3
Author(s): 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
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.

Graphical abstract

Teaser

When undifferentiated spermatogonia enter differentiation, they go through meiotic recombination followed by histone-protamine transition, eventually to become highly specialized haploid cells called spermatozoa. Ueda et al. reveal a testis-specific histone variant H3t that enables nucleosomes to form an open chromatin structure and is essential for the initial step of spermatogenesis. H3t deficiency leads to azoospermia.


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