Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability
Ziqian Min,
Huan Xin,
Xiaowen Liu,
Jingyu Wan,
Ziling Fan,
Xinxu Rao,
Jiahui Fan,
Lifang Yang,
Dan Li
Affiliations
Ziqian Min
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Huan Xin
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Xiaowen Liu
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Jingyu Wan
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Ziling Fan
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Xinxu Rao
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Jiahui Fan
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China
Lifang Yang
Cancer Research Institute, Xiangya School of Medicine, Central South University, 410078 Changsha, China
Dan Li
Department of Life Science, College of Biology, Hunan University, 410012 Changsha, China; Shenzhen Research Institute of Hunan University, 518000 Shenzhen, China; Corresponding author
Summary: Chromodomain helicase DNA-binding domain 2 (CHD2) is a chromatin remodeling factor involved in many developmental processes. However, its role in male germ cell development has not been elucidated. Here, we confirm that CHD2 expression is enriched in the male germline. In a heterozygous knockout mouse model of Chd2 (Chd2+/−), we demonstrated that Chd2 haploinsufficiency resulted in testicular developmental delay, an increased rate of abnormal sperm, and impaired fertility in mice. In vitro experiments in mouse spermatogonia showed that CHD2 knockdown inhibits spermatogonial self-renewal. Mechanistically, CHD2 maintains the enrichment of H3K4me3 in the Ccnb1 and Ccnd2 promotors, consequently promoting the transcription of Ccnb1 and Ccnd2. In addition, CHD2 interacts with the cleavage stimulation factor CSTF3 and upregulates the expression of OCT4 and PLZF by improving mRNA stability. This is the first study to reveal the role and mechanism of CHD2 in maintaining spermatogonial self-renewal.
