HANP1/H1T2, a Novel Histone H1-Like Protein Involved in Nuclear Formation and Sperm Fertility
HANP1/H1T2, a Novel Histone H1-Like Protein Involved in Nuclear Formation and Sperm Fertility
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DOI：
10.1128/mcb.25.16.7107-7119.2005
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发表时间：
2005-08
影响因子：
5.3
通讯作者：
Hiromitsu Tanaka;N. Iguchi;A. Isotani;K. Kitamura;Y. Toyama;Y. Matsuoka;M. Onishi;K. Masai;M. Maekawa;K. Toshimori;M. Okabe;Y. Nishimune
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文献类型：
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作者：
Hiromitsu Tanaka;N. Iguchi;A. Isotani;K. Kitamura;Y. Toyama;Y. Matsuoka;M. Onishi;K. Masai;M. Maekawa;K. Toshimori;M. Okabe;Y. Nishimune
摘要我们从小鼠睾丸中克隆了一个睾丸特异性cDNA，它编码一个组蛋白H1样的单倍体生殖细胞特异性核蛋白，命名为HANP 1/H1 T2。HANP 1/H1 T2蛋白特异性定位于小鼠精子细胞的细胞核在分化步骤5至13，但不成熟精子的细胞核。HANP 1/H1 T2含有一个富含丝氨酸的结构域和一个ATP/GTP结合位点，它与DNA、ATP和鱼精蛋白结合。为了研究HANP 1/H1 T2的生理作用，我们产生了HANP 1/H1 T2破坏的突变小鼠。纯合子Hanp 1/H1 T2突变男性不育，但女性生育。虽然从附睾中回收了大量精子，但其形状和功能均异常。在精子形态发生过程中，细胞核的形成受到干扰，精蛋白-1和-2在细胞核中只能微弱地检测到。染色质包装是异常的，通过电子显微镜和生化分析证明。突变精子表现出缺乏活力，在体外受精条件下不能使卵子受精;然而，它们能够通过胞浆内单精子注射使卵子受精，从而产生健康后代。因此，我们发现，HANP 1/H1 T2是必不可少的核形成的功能精子，特别是在精子发生过程中的组蛋白与鱼精蛋白的替代。在提交手稿的时候，我们发现了一个独立的出版物，由Martianov等人。Martianov，S.布兰科西尼河Catena，A.甘斯穆勒，N.科塔亚湾Parvinen，P. Sassone-Corsi，and I. Davidson，Proc. Natl. Acad. Sci. USA 102：2808-2813，2005），其报道了类似的结果。
ABSTRACT We cloned a testis-specific cDNA from mice that encodes a histone H1-like, haploid germ cell-specific nuclear protein designated HANP1/H1T2. The HANP1/H1T2 protein was specifically localized to the nuclei of murine spermatids during differentiation steps 5 to 13 but not to the nuclei of mature sperm. HANP1/H1T2 contains an arginine-serine-rich domain and an ATP/GTP binding site, and it binds to DNA, ATP, and protamine. To investigate the physiological role of HANP1/H1T2, we generated Hanp1/H1T2-disrupted mutant mice. Homozygous Hanp1/H1T2 mutant males were infertile, but females were fertile. Although a substantial number of sperm were recovered from the epididymides, their shape and function were abnormal. During sperm morphogenesis, the formation of nuclei was disturbed and protamine-1 and -2 were only weakly detectable in the nuclei. The chromatin packaging was aberrant, as demonstrated by electron microscopy and biochemical analysis. The mutant sperm exhibited deficient motility and were not competent to fertilize eggs under in vitro fertilization conditions; however, they were capable of fertilizing eggs via intracytoplasmic sperm injection that resulted in the birth of healthy progeny. Thus, we found that HANP1/H1T2 is essential for nuclear formation in functional spermatozoa and is specifically involved in the replacement of histones with protamines during spermiogenesis. At the time of submission of the manuscript, we found an independent publication by Martianov et al. (I. Martianov, S. Brancorsini, R. Catena, A. Gansmuller, N. Kotaja, M. Parvinen, P. Sassone-Corsi, and I. Davidson, Proc. Natl. Acad. Sci. USA 102:2808-2813, 2005) that reported similar results.