Dai Lei, Endo Daisuke, Akiyama Naotaro, Yamamoto-Fukuda Tomomi, Koji Takehiko
Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan.
Histochem Cell Biol. 2015 Feb;143(2):209-24. doi: 10.1007/s00418-014-1283-1. Epub 2014 Oct 19.
Histone acetylation is involved in the regulation of chromatin structure and gene function. We reported previously that histone H3 acetylation pattern is subject to dynamic changes and limited to certain stages of germ cell differentiation during murine spermatogenesis, suggesting a crucial role for acetylation in the process. In the present study, we investigated the effects of hyper- and hypo-acetylation on spermatogenesis. Changes in acetylation level were induced by either in vivo administration of sodium phenylbutyrate, a histone deacetylase inhibitor, or by knockdown of histone acetyltransferases using short hairpin RNA plasmids transfection. Administration of sodium phenylbutyrate induced accumulation of acetylated histone H3 at lysine 9 and lysine 18 in round spermatids, together with spermatid morphological abnormalities and induction of apoptosis through a Bax-related pathway. Knockdown of steroid receptor coactivator 1, a member of histone acetyltransferases, but not general control of amino acid synthesis 5 nor elongator protein 3 by in vivo electroporation of shRNA plasmids, reduced acetylated histone H3 at lysine 9 in round spermatids, and induced morphological abnormalities. We concluded that the proper regulation of histone H3 acetylation levels is important for spermatid differentiation and complex chromatin remodeling during spermiogenesis.
组蛋白乙酰化参与染色质结构和基因功能的调控。我们先前报道，在小鼠精子发生过程中，组蛋白H3乙酰化模式会发生动态变化，且仅限于生殖细胞分化的特定阶段，这表明乙酰化在此过程中起关键作用。在本研究中，我们研究了高乙酰化和低乙酰化对精子发生的影响。通过体内给予组蛋白去乙酰化酶抑制剂苯丁酸钠，或使用短发夹RNA质粒转染敲低组蛋白乙酰转移酶来诱导乙酰化水平的变化。给予苯丁酸钠会诱导圆形精子细胞中赖氨酸9和赖氨酸18处乙酰化组蛋白H3的积累，同时伴有精子细胞形态异常，并通过与Bax相关的途径诱导细胞凋亡。通过体内电穿孔shRNA质粒敲低组蛋白乙酰转移酶成员类固醇受体辅激活因子1，但不敲低氨基酸合成通用控制因子5或延伸因子3，会降低圆形精子细胞中赖氨酸9处乙酰化组蛋白H3的水平，并诱导形态异常。我们得出结论，组蛋白H3乙酰化水平的适当调节对于精子细胞分化和精子形成过程中复杂的染色质重塑很重要。
