Institute of Molecular Biology of Barcelona, CSIC, Baldiri Reixac, 4, 08028 Barcelona, Spain; Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute for Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Institute for Research in Biomedicine, IRB Barcelona, The Barcelona Institute for Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain.
Cell Rep. 2017 Dec 12;21(11):3178-3189. doi: 10.1016/j.celrep.2017.11.060.
Drosophila spermatogenesis constitutes a paradigmatic system to study maintenance, proliferation, and differentiation of adult stem cell lineages. Each Drosophila testis contains 6-12 germ stem cells (GSCs) that divide asymmetrically to produce gonialblast cells that undergo four transit-amplifying (TA) spermatogonial divisions before entering spermatocyte differentiation. Mechanisms governing these crucial transitions are not fully understood. Here, we report the essential role of the germline linker histone dBigH1 during early spermatogenesis. Our results suggest that dBigH1 is a general silencing factor that represses Bam, a key regulator of spermatogonia proliferation that is silenced in spermatocytes. Reciprocally, Bam represses dBigH1 during TA divisions. This double-repressor mechanism switches dBigH1/Bam expression from off/on in spermatogonia to on/off in spermatocytes, regulating progression into spermatocyte differentiation. dBigH1 is also required for GSC maintenance and differentiation. These results show the critical importance of germline H1s for male GSC lineage differentiation, unveiling a regulatory interaction that couples transcriptional and translational repression.
果蝇精子发生构成了研究成体干细胞谱系维持、增殖和分化的典范系统。每个果蝇睾丸包含 6-12 个生殖干细胞 (GSCs)，它们不对称分裂产生精原母细胞，这些细胞在进入精母细胞分化之前经历四个过渡扩增 (TA) 精原细胞分裂。控制这些关键转变的机制尚未完全了解。在这里，我们报告了生殖系连接组蛋白 dBigH1 在早期精子发生中的重要作用。我们的结果表明，dBigH1 是一种通用的沉默因子，可抑制 Bam，这是一种调控精原细胞增殖的关键调节因子，在精母细胞中被沉默。反之，Bam 在 TA 分裂过程中抑制 dBigH1。这种双重抑制剂机制将 dBigH1/Bam 的表达从精原细胞中的关闭/开启切换到精母细胞中的开启/关闭，从而调节进入精母细胞分化。dBigH1 也需要维持和分化 GSC。这些结果表明生殖系 H1s 对雄性 GSC 谱系分化至关重要，揭示了一种调节转录和翻译抑制的相互作用。
