Howard Hughes Medical Institute, Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
Dev Cell. 2022 May 9;57(9):1102-1118.e7. doi: 10.1016/j.devcel.2022.04.007. Epub 2022 Apr 27.
During Drosophila melanogaster male germline stem cell (GSC) asymmetric division, preexisting old versus newly synthesized histones H3 and H4 are asymmetrically inherited. However, the biological outcomes of this phenomenon have remained unclear. Here, we tracked old and new histones throughout the GSC cell cycle through the use of high spatial and temporal resolution microscopy. We found unique features that differ between old and new histone-enriched sister chromatids, including differences in nucleosome density, chromosomal condensation, and H3 Ser10 phosphorylation. These distinct chromosomal features lead to their differential association with Cdc6, a pre-replication complex component, and subsequent asynchronous DNA replication initiation in the resulting daughter cells. Disruption of asymmetric histone inheritance abolishes differential Cdc6 association and asynchronous S-phase entry, demonstrating that histone asymmetry acts upstream of these critical cell-cycle progression events. Furthermore, disruption of these GSC-specific chromatin features leads to GSC defects, indicating a connection between histone inheritance, cell-cycle progression, and cell fate determination.
在黑腹果蝇雄性生殖干细胞（GSC）不对称分裂过程中，预先存在的旧与新合成的组蛋白 H3 和 H4 呈不对称遗传。然而，这一现象的生物学后果仍不清楚。在这里，我们通过使用高时空分辨率显微镜，在整个 GSC 细胞周期中追踪新旧组蛋白。我们发现，在富含旧和新组蛋白的姐妹染色单体之间存在独特的特征差异，包括核小体密度、染色体凝聚和 H3 Ser10 磷酸化的差异。这些不同的染色体特征导致它们与复制前复合物成分 Cdc6 的不同结合，并在随后的子细胞中导致异步 DNA 复制起始。不对称组蛋白遗传的破坏会导致 Cdc6 结合的差异和 S 期进入的异步，这表明组蛋白不对称性作用于这些关键细胞周期进程事件的上游。此外，破坏这些 GSC 特异性染色质特征会导致 GSC 缺陷，表明组蛋白遗传、细胞周期进程和细胞命运决定之间存在联系。
