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Chromodomain Helicase DNA-binding Domain 2 Maintains Spermatogonial Self-renewal by Promoting Chromatin Accessibility and MRNA Stability

Overview
Journal iScience
Publisher Cell Press
Date 2022 Nov 29
PMID 36444304
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Abstract

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 ( ), we demonstrated that haploinsufficiency resulted in testicular developmental delay, an increased rate of abnormal sperm, and impaired fertility in mice. experiments in mouse spermatogonia showed that CHD2 knockdown inhibits spermatogonial self-renewal. Mechanistically, CHD2 maintains the enrichment of H3K4me3 in the and promotors, consequently promoting the transcription of and . 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.

Citing Articles

Chromatin remodeler CHD8 is required for spermatogonial proliferation and early meiotic progression.

Nitahara K, Kawamura A, Kitamura Y, Kato K, Namekawa S, Nishiyama M Nucleic Acids Res. 2024; 52(6):2995-3010.

PMID: 38224953 PMC: 11014243. DOI: 10.1093/nar/gkad1256.

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