AUTHOR=Li Xueliang , Chen Xiaoxu , Liu Yingdong , Zhang Pengfei , Zheng Yi , Zeng Wenxian 

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

JOURNAL=Frontiers in Genetics

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2020.00997

DOI=10.3389/fgene.2020.00997

ISSN=1664-8021

ABSTRACT=<p>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 of <italic>Setdb1</italic> impaired cell proliferation, led to an increase in reactive oxygen species (ROS) level through NADPH oxidase, and <italic>Setdb1</italic> deficiency activated ROS downstream signaling pathways, including JNK and p38 MAPK, which possibly contributed to SSC apoptosis. Melatonin scavenged ROS and rescued the phenotype of <italic>Setdb1</italic> KD. In addition, we demonstrated that SETDB1 regulated NADPH oxidase 4 (<italic>Nox4</italic>) and <italic>E2F1</italic>. Therefore, this study uncovers the new roles of SETDB1 in mediating intracellular ROS homeostasis for the survival of SSC.</p>