Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.

Differential condensation of sister chromatids acts with Cdc6 to ensure asynchronous S-phase entry in Drosophila male germline stem cell lineage.
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DOI:
10.1016/j.devcel.2022.04.007
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发表时间:
2022-05-09
期刊:
影响因子:
11.8
通讯作者:
Chen, Xin
Chen, Xin
中科院分区:
生物学1区
文献类型:
--
作者:
Ranjan, Rajesh;Snedeker, Jonathan;Wooten, Matthew;Chu, Carolina;Bracero, Sabrina;Mouton, Taylar;Chen, Xin

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在果蝇雄性生殖干细胞(GSC)不对称分裂过程中,先前存在的旧组蛋白H3和新合成的组蛋白H4是不对称遗传的。然而,这一现象的生物学后果仍不清楚。在这里,我们通过使用高空间和时间分辨率显微镜跟踪整个GSC细胞周期的新旧组蛋白。我们发现了新旧富含组蛋白的姐妹染色单体之间存在差异的独特特征,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Cdc6(复制前复合物组分)的差异关联,以及随后在所得子细胞中的异步DNA复制起始。不对称组蛋白遗传的破坏废除差异Cdc6协会和异步S期进入,表明组蛋白不对称行为的上游这些关键的细胞周期进展事件。此外,这些GSC特异性染色质特征的破坏导致GSC缺陷,表明组蛋白遗传、细胞周期进展和细胞命运决定之间存在联系。果蝇雄性生殖干细胞(GSC)经历不对称细胞分裂。Ranjan等人发现GSC姐妹染色单体在核小体密度、染色体浓缩和H3 Ser10磷酸化方面不同。这些独特的特征导致它们差异地招募关键的复制组件,导致随后的细胞周期的异步启动。
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. Drosophila male germline stem cells (GSCs) undergo asymmetric cell division. Ranjan et al. find that GSC sister chromatids differ in nucleosome density, chromosomal condensation, and H3 Ser10 phosphorylation. These distinct features cause them to differentially recruit a key replication component, leading to asynchronous initiation of the subsequent cell cycle.
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