Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-23378-4
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Funding
- program of the Joint Usage/Research Center for Developmental Medicine, IMEG, Kumamoto University
- KAKENHI [19K06642, 20K22638]
- Takeda Science Foundation
- MEXT Japan [17H03634, 18K19304, 19H05245, 19H05743, 20H03265, 20K21504, JP 16H06276]
- Institute of Advanced Medical Sciences, Tokushima University [30-A-7]
- Sumitomo Foundation
- Naito Foundation
- Astellas Foundation for Research on Metabolic Disorders
- Daiichi Sankyo Foundation of Life Science
- Uehara Memorial Foundation
- NOVARTIS Foundation (Japan) for the promotion of Science
- Grants-in-Aid for Scientific Research [19K06642, 19H05245, 20K22638, 20K21504, 20H03265, 19H05743, 18K19304, 17H03634] Funding Source: KAKEN
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The study identified a protein complex composed of ZFP541 and KCTD19 as key transcriptional regulators in mouse meiotic prophase progression. This complex promotes the completion of meiotic prophase and triggers the reconstruction of transcriptional network and chromatin organization. ZFP541 binds to and suppresses genes associated with transcriptional regulation and covalent chromatin modification to ensure proper meiotic progression.
During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development. The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.
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