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

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 Setdb1 impaired cell proliferation, led to an increase in r...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Xueliang, Chen, Xiaoxu, Liu, Yingdong, Zhang, Pengfei, Zheng, Yi, Zeng, Wenxian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Genetics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567028/
https://www.ncbi.nlm.nih.gov/pubmed/33133132
http://dx.doi.org/10.3389/fgene.2020.00997
_version_ 1783596239286173696
author Li, Xueliang
Chen, Xiaoxu
Liu, Yingdong
Zhang, Pengfei
Zheng, Yi
Zeng, Wenxian
author_facet Li, Xueliang
Chen, Xiaoxu
Liu, Yingdong
Zhang, Pengfei
Zheng, Yi
Zeng, Wenxian
author_sort Li, Xueliang
collection PubMed
description 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 Setdb1 impaired cell proliferation, led to an increase in reactive oxygen species (ROS) level through NADPH oxidase, and Setdb1 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 Setdb1 KD. In addition, we demonstrated that SETDB1 regulated NADPH oxidase 4 (Nox4) and E2F1. Therefore, this study uncovers the new roles of SETDB1 in mediating intracellular ROS homeostasis for the survival of SSC.
format Online
Article
Text
id pubmed-7567028
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-75670282020-10-30 The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase Li, Xueliang Chen, Xiaoxu Liu, Yingdong Zhang, Pengfei Zheng, Yi Zeng, Wenxian Front Genet Genetics 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 Setdb1 impaired cell proliferation, led to an increase in reactive oxygen species (ROS) level through NADPH oxidase, and Setdb1 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 Setdb1 KD. In addition, we demonstrated that SETDB1 regulated NADPH oxidase 4 (Nox4) and E2F1. Therefore, this study uncovers the new roles of SETDB1 in mediating intracellular ROS homeostasis for the survival of SSC. Frontiers Media S.A. 2020-10-02 /pmc/articles/PMC7567028/ /pubmed/33133132 http://dx.doi.org/10.3389/fgene.2020.00997 Text en Copyright © 2020 Li, Chen, Liu, Zhang, Zheng and Zeng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Li, Xueliang
Chen, Xiaoxu
Liu, Yingdong
Zhang, Pengfei
Zheng, Yi
Zeng, Wenxian
The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title_full The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title_fullStr The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title_full_unstemmed The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title_short The Histone Methyltransferase SETDB1 Modulates Survival of Spermatogonial Stem/Progenitor Cells Through NADPH Oxidase
title_sort histone methyltransferase setdb1 modulates survival of spermatogonial stem/progenitor cells through nadph oxidase
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567028/
https://www.ncbi.nlm.nih.gov/pubmed/33133132
http://dx.doi.org/10.3389/fgene.2020.00997
work_keys_str_mv AT lixueliang thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT chenxiaoxu thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT liuyingdong thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zhangpengfei thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zhengyi thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zengwenxian thehistonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT lixueliang histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT chenxiaoxu histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT liuyingdong histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zhangpengfei histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zhengyi histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase
AT zengwenxian histonemethyltransferasesetdb1modulatessurvivalofspermatogonialstemprogenitorcellsthroughnadphoxidase

Ejemplares similares