Ueda Jun, Harada Akihito, Urahama Takashi, Machida Shinichi, Maehara Kazumitsu, Hada Masashi, Makino Yoshinori, Nogami Jumpei, Horikoshi Naoki, Osakabe Akihisa, Taguchi Hiroyuki, Tanaka Hiroki, Tachiwana Hiroaki, Yao Tatsuma, Yamada Minami, Iwamoto Takashi, Isotani Ayako, Ikawa Masahito, Tachibana Taro, Okada Yuki, Kimura Hiroshi, Ohkawa Yasuyuki, Kurumizaka Hitoshi, Yamagata Kazuo
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.
Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Cell Rep. 2017 Jan 17;18(3):593-600. doi: 10.1016/j.celrep.2016.12.065.
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.
细胞分化与建立细胞类型特异性表观基因组景观过程中的动态染色质重塑相关。在此，我们发现小鼠睾丸特异性且依赖复制的组蛋白H3变体H3t对精子发生的早期阶段至关重要。H3t基因缺陷导致无精子症，原因是单倍体生殖细胞的缺失。在正常精子发生过程中，当分化的精原细胞出现时，H3t出现并取代了经典的H3蛋白。结构和生化分析表明，含有H3t的核小体比经典核小体更具柔韧性。因此，通过在精原细胞分化过程中将H3t整合到基因组中，雄性生殖细胞能够进入减数分裂及后续阶段。
