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| Status |
Public on Sep 02, 2024 |
| Title |
A non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Male infertility can be caused by chromosomal abnormalities, mutations, and epigenetic defects. Epigenetic modifiers pre-program hundreds of spermatogenic genes in spermatogonial stem cells (SSCs) for expression later in spermatids, but it remains mostly unclear whether and how those genes are involved in fertility. Here, we report that Wfdc15a, a WFDC family protease inhibitor pre-programmed by KMT2B, is essential for spermatogenesis. We found that Wfdc15a is a non-canonical bivalent gene carrying both H3K4me3 and facultative H3K9me3 in SSCs but is later activated along with the loss of H3K9me3 and acquisition of H3K27ac during meiosis. We show that WFDC15A deficiency causes defective spermiogenesis at the beginning of spermatid elongation. Notably, depletion of WFDC15A causes substantial disturbance of the testicular protease-antiprotease network and leads to an orchitis-like inflammatory response associated with TNFa expression in round spermatids. Together, our results reveal a unique epigenetic program regulating innate immunity crucial for fertility.
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| Overall design |
RNA-seq analysis of Wfdc15a control (+/+ and +/-) and knockout (-/-) mouse round spermatids.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/39222051/
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| Contributor(s) |
Tomizawa S, Ohbo K |
| Citation(s) |
39222051 |
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| Submission date |
Jan 13, 2023 |
| Last update date |
Sep 30, 2024 |
| Contact name |
Shin-ichi Tomizawa |
| Organization name |
Yokohama City University
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| Department |
School of Medicine
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| Lab |
Histology
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| Street address |
3-9 Fukuura, Kanazawa-ku
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| City |
Yokohama |
| State/province |
Kanagawa |
| ZIP/Postal code |
236-0004 |
| Country |
Japan |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA923583 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE222806_Wfdc15aRST_Log2RPM.txt.gz |
710.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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