Regulation of DNA replication time is crucial for appropriate gene expression

Eukaryotic genomes are replicated in a reproducible temporal order, however, the physiological significance is poorly understood. We compared replication dynamics in divergent yeast species and identified genomic features with conserved replication times. Histone genes were amongst the earliest replicating loci in all species. We delayed the replication of HTA1-HTB1 and discovered that this halved the histone gene expression. Finally, we show that histone and cell cycle genes in general are exempt from dosage compensation mechanisms. Thus we have uncovered one of the first physiological requirements for regulated replication time and demonstrate a direct link between replication time and gene expression.真核生物基因组以可重现的时间顺序进行复制，但其生理意义至今仍不甚明确。本研究对亲缘关系较远的酵母物种的复制动态开展比较分析，鉴定出了复制时间具有保守性的基因组特征。组蛋白基因在所有被测物种中均属于最早完成复制的基因座之一。我们延迟了HTA1-HTB1的复制过程，结果发现该操作使组蛋白基因的表达量降低了一半。最后，本研究证实，组蛋白基因与细胞周期基因总体上可免于剂量补偿机制的调控。综上，本研究首次揭示了受调控的复制时间所具备的首批生理需求之一，并证实了复制时间与基因表达之间存在直接关联。