The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase

被引:5
|
作者
Li, Xueliang [1 ]
Chen, Xiaoxu [1 ]
Liu, Yingdong [1 ]
Zhang, Pengfei [1 ]
Zheng, Yi [1 ]
Zeng, Wenxian [1 ]
机构
[1] Northwest A&F Univ, Coll Anim Sci & Technol, Key Lab Anim Genet Breeding & Reprod Shaanxi Prov, Yangling, Shaanxi, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金;
关键词
SETDB1; NOX4; ROS; spermatogonial stem cell; FOXO TRANSCRIPTION FACTORS; OXIDATIVE STRESS; REACTIVE OXYGEN; UP-REGULATION; NOX4; APOPTOSIS; ROS; ACTIVATION; EXPRESSION; DAF-16;
D O I
10.3389/fgene.2020.00997
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
SETDB1, a histone H3 lysine 9 (H3K9) methyltransferase, is crucial in meiosis and embryo development. This study aimed to investigate whether SETDB1 was associated with spermatogonial stem cells (SSC) homeostasis. We found that knockdown ofSetdb1impaired cell proliferation, led to an increase in reactive oxygen species (ROS) level through NADPH oxidase, andSetdb1deficiency activated ROS downstream signaling pathways, including JNK and p38 MAPK, which possibly contributed to SSC apoptosis. Melatonin scavenged ROS and rescued the phenotype ofSetdb1KD. In addition, we demonstrated that SETDB1 regulated NADPH oxidase 4 (Nox4) andE2F1. Therefore, this study uncovers the new roles of SETDB1 in mediating intracellular ROS homeostasis for the survival of SSC.
引用
收藏
页数:12
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