EZH2 deletion promotes spermatogonial differentiation and apoptosis

被引:32
作者
Jin, Cheng [1 ,2 ]
Zhang, Yan [1 ,3 ]
Wang, Zhi-Peng [1 ,2 ]
Wang, Xiu-Xia [1 ]
Sun, Tie-Cheng [1 ,2 ]
Li, Xiao-Yu [1 ,2 ]
Tang, Xin [1 ,2 ]
Cheng, Jin-Mei [1 ,2 ]
Li, Jian [1 ,2 ]
Chen, Su-Ren [1 ]
Deng, Shou-Long [1 ]
Liu, Yi-Xun [1 ]
机构
[1] Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing, Peoples R China
[2] Univ Chinese Acad Sci, Beijing, Peoples R China
[3] Changsha Reprod Med Hosp, Changsha, Hunan, Peoples R China
基金
中国国家自然科学基金;
关键词
STEM-CELL COMPARTMENTS; GERMLINE TRANSMISSION; DOWN-REGULATION; RETINOIC ACID; VITAMIN-A; PROLIFERATION; EXPRESSION; SPERMATOGENESIS; IDENTIFICATION; MAINTENANCE;
D O I
10.1530/REP-17-0302
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Spermatogenesis is crucial for male fertility and is therefore tightly controlled by a variety of epigenetic regulators. However, the function of enhancer of zeste homolog 2 (EZH2) in spermatogenesis and the molecular mechanisms underlying its activity remain poorly defined. Here, we demonstrate that deleting EZH2 promoted spermatogonial differentiation and apoptosis. EZH2 is expressed in spermatogonia, spermatocytes and round and elongated spermatids from stage 9 to 11 but not in leptotene and zygotene spermatocytes. Knocking down Ezh2 in vitro using a lentivirus impaired self-renewal in spermatogonial stem cells (SSCs), and the conditional knockout of Ezh2 in spermatogonial progenitors promoted precocious spermatogonial differentiation. EZH2 functions to balance self-renewal and differentiation in spermatogonia by suppressing NEUROG3 and KIT via a direct interaction that is independent of its histone methyltransferase activity. Moreover, deleting Ezh2 enhanced the activation of CASP3 in spermatids, resulting in reduced spermatozoa production. Collectively, these data demonstrate that EZH2 plays a nonclassical role in the regulation of spermatogonial differentiation and apoptosis in murine spermatogenesis.
引用
收藏
页码:615 / 625
页数:11
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