Matsui Masaya, Kawaguchi Shinichi, Kai Toshie
Graduate School of Frontier Biosciences, The University of Osaka, Osaka 565-0871, Japan.
Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
bioRxiv. 2025 Jun 3:2025.05.17.654630. doi: 10.1101/2025.05.17.654630.
Apoptosis plays a central role in shaping tissues and preserving cellular integrity across developmental stages. In the germline, its precise regulation is critical to ensure both the elimination of aberrant cells and the maintenance of reproductive capacity. However, the molecular mechanisms that control apoptotic susceptibility in germline cells remain poorly defined. Here, we identify () as a female germline-specific regulator of apoptosis in . Loss of leads to near-complete depletion of germline cells at the time of eclosion, associated with upregulation of the pro-apoptotic gene () and activation of caspase-dependent cell death. Reporter assays in S2 cells show that Stil directly represses transcription through its N-terminal BED-type zinc finger domain. Despite the absence of , undifferentiated germline cells remain resistant to apoptosis. Analysis of publicly available chromatin data reveals that the locus in these cells resides in a closed, H3K9me3-enriched chromatin state, suggesting a Stil-independent mode of transcriptional silencing. Together, our findings uncover two distinct mechanisms that protects the female germline from -dependent apoptosis: Stil-mediated transcriptional repression that operates in both undifferentiated and differentiated germline cells, and an additional chromatin-based silencing mechanism that functions specifically in undifferentiated cells. This work provides new insights into the interplay between transcriptional and chromatin-based regulations that maintain germline cell identity and survival.
凋亡在组织形成和维持发育各阶段细胞完整性方面发挥着核心作用。在生殖系中,其精确调控对于确保异常细胞的清除和生殖能力的维持至关重要。然而,控制生殖系细胞凋亡易感性的分子机制仍不清楚。在这里,我们确定()为()中生殖系特异性的凋亡调节因子。()的缺失导致羽化时生殖系细胞几乎完全耗尽,这与促凋亡基因()的上调和半胱天冬酶依赖性细胞死亡的激活有关。在S2细胞中的报告基因检测表明,Stil通过其N端BED型锌指结构域直接抑制()转录。尽管缺乏(),未分化的生殖系细胞仍对凋亡具有抗性。对公开可用的染色质数据的分析表明,这些细胞中的()基因座处于封闭的、富含H3K9me3的染色质状态,这表明存在一种不依赖Stil的转录沉默模式。总之,我们的研究结果揭示了两种不同的机制来保护雌性生殖系免受()依赖性凋亡:Stil介导的转录抑制作用于未分化和分化的生殖系细胞,以及一种额外的基于染色质的沉默机制,该机制专门在未分化细胞中起作用。这项工作为维持生殖系细胞身份和存活的转录调控与基于染色质的调控之间的相互作用提供了新的见解。