DREAM 复合体因子 TCX5/6 在体细胞中抑制减数分裂双链断裂形成以维持基因组稳定性
Suppression of meiotic double-strand break formation in somatic cells by DREAM factors TCX5/6 maintains genome stability
摘要
该研究以减数分裂特异基因 DMC1 的启动子为诱饵，在植物（拟南芥）体系中鉴定出 DREAM 复合体组分 TCX5 与 TCX6，它们可在体细胞中直接抑制 DMC1 等减数分裂基因的转录。转录组分析显示 tcx5/6 突变体叶片中减数分裂基因广泛异位上调；相应体细胞出现 DNA 双链断裂，并对 DNA 损伤超敏。遗传学分析表明，SPO11-1 对异位减数分裂基因激活并非必需，但对突变体体细胞的 DNA 损伤应答必不可少；机制上 TCX5/6 通过 H3K4me3 修饰实现抑制。该工作揭示了体细胞中抑制减数分裂重组、防止基因组不稳定的新机制。
原文摘要
Meiotic recombination in reproductive cells is initiated by DNA double-strand breaks (DSBs) and requires the expression of meiosis-specific genes, yet how the transcription of those genes is regulated in either meiotic or somatic cells remains unclear. Here, using a representative meiosis-specific DMC1 gene promoter as a bait, we identified two DREAM factors TCX5 and TCX6 required for direct repression of DMC1 in somatic cells. Transcriptomic analyses show broad ectopic up-regulation of meiotic genes in tcx5/6 leaves. Consistently, tcx5/6 somatic cells form DSBs and exhibit hypersensitivity to DNA damage compared to wild type. Further genetic analyses reveal that SPO11-1 is dispensable for ectopic meiotic gene activation but essential for the DNA damage response in tcx5/6 somatic cells. Last, we demonstrated that TCX5/6 repress meiotic gene expression through H3K4me3 modification. This finding uncovers an unexpected mechanism for suppressing meiotic recombination in somatic cells, thus preventing genetic diversity and genome instability in organisms.
推荐理由：机制新颖、证据链完整（遗传学、转录组和修饰层面相互印证），但研究对象为植物体细胞，与人类生殖与辅助生殖的直接关联较弱，主要作为“减数分裂基因体细胞沉默与基因组稳定性”的交叉参考阅读。
文献解读
尚未生成。