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A non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis

GSE222806 Mus musculus Expression profiling by high throughput sequencing 4 samples Submitted 2024/09/02 Platform GPL17021
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.
Published in
The non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis
Tomizawa SI, Fellows R, Ono M et al. · Development (Cambridge, England) 2024 · PMID 39222051 · doi:10.1242/dev.202834
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Also filed as BioProject PRJNA923583 and SRA study SRP417330. Searching any of these in the dataset finder brings you back here.

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