Global early replication disrupts gene expression and chromatin conformation in a single cell cycle.
Global early replication disrupts gene expression and chromatin conformation in a single cell cycle.
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DOI：
10.1186/s13059-022-02788-7
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发表时间：
2022-10-17
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影响因子：
12.3
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中科院分区：
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许多生物的早期胚胎分裂，包括鱼、蝇和青蛙，其特征是由高复制起始率引起的非常快速的s期。在体细胞中，由于起始事件总数的减少和起始激活的时间顺序的强加，s期更长。s期复制起始速率和时间变化的生理重要性尚不清楚。在这里，我们利用出芽酵母中的条件系统来评估复制起始的时间控制的重要性，以驱动单细胞周期中大多数起源的早期复制。我们发现，全球早期复制破坏了超过四分之一的基因的表达。通过删除单个起源，我们发现延迟复制足以恢复正常的基因表达，直接暗示了在这种调节中起源激活控制。全局早期复制在s期破坏核小体定位和转录因子结合，表明s期速率对调节染色质景观很重要。总之，这些数据提供了新的见解，在早期胚胎中，在协调复制、基因表达和染色质建立的s期起源放电的时间控制的作用。在线版本包含补充材料，下载地址：10.1186/s13059-022-02788-7。
The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo. The online version contains supplementary material available at 10.1186/s13059-022-02788-7.