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Publication : Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability.

First Author  Min Z Year  2022
Journal  iScience Volume  25
Issue  12 Pages  105552
PubMed ID  36444304 Mgi Jnum  J:334223
Mgi Id  MGI:7397851 Doi  10.1016/j.isci.2022.105552
Citation  Min Z, et al. (2022) Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability. iScience 25(12):105552
abstractText  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.
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