Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability
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 kno...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-12-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222018247 |
| _version_ | 1811304752773857280 |
|---|---|
| author | Ziqian Min Huan Xin Xiaowen Liu Jingyu Wan Ziling Fan Xinxu Rao Jiahui Fan Lifang Yang Dan Li |
| author_facet | Ziqian Min Huan Xin Xiaowen Liu Jingyu Wan Ziling Fan Xinxu Rao Jiahui Fan Lifang Yang Dan Li |
| author_sort | Ziqian Min |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T08:12:57Z |
| format | Article |
| id | doaj.art-decfc2ca6c884a1da2bedf423f1b4a27 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T08:12:57Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-decfc2ca6c884a1da2bedf423f1b4a272022-12-22T02:54:53ZengElsevieriScience2589-00422022-12-012512105552Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stabilityZiqian Min0Huan Xin1Xiaowen Liu2Jingyu Wan3Ziling Fan4Xinxu Rao5Jiahui Fan6Lifang Yang7Dan Li8Department of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, ChinaCancer Research Institute, Xiangya School of Medicine, Central South University, 410078 Changsha, ChinaDepartment of Life Science, College of Biology, Hunan University, 410012 Changsha, China; Shenzhen Research Institute of Hunan University, 518000 Shenzhen, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004222018247Biological sciencesmolecular mechanism of gene regulationcell biologytranscriptomicsalternate contact |
| spellingShingle | Ziqian Min Huan Xin Xiaowen Liu Jingyu Wan Ziling Fan Xinxu Rao Jiahui Fan Lifang Yang Dan Li Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability iScience Biological sciences molecular mechanism of gene regulation cell biology transcriptomics alternate contact |
| title | Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability |
| title_full | Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability |
| title_fullStr | Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability |
| title_full_unstemmed | Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability |
| title_short | Chromodomain helicase DNA-binding domain 2 maintains spermatogonial self-renewal by promoting chromatin accessibility and mRNA stability |
| title_sort | chromodomain helicase dna binding domain 2 maintains spermatogonial self renewal by promoting chromatin accessibility and mrna stability |
| topic | Biological sciences molecular mechanism of gene regulation cell biology transcriptomics alternate contact |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222018247 |
| work_keys_str_mv | AT ziqianmin chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT huanxin chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT xiaowenliu chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT jingyuwan chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT zilingfan chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT xinxurao chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT jiahuifan chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT lifangyang chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability AT danli chromodomainhelicasednabindingdomain2maintainsspermatogonialselfrenewalbypromotingchromatinaccessibilityandmrnastability |