Expression homeostasis during DNA replication
Expression homeostasis during DNA replication
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DOI：
10.1126/science.aad1162
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发表时间：
2016-03
期刊：
影响因子：
56.9
通讯作者：
Yoav Voichek;Raz Bar-Ziv;N. Barkai
中科院分区：
文献类型：
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作者：
Yoav Voichek;Raz Bar-Ziv;N. Barkai
当基因组复制时，在细胞分裂之前，基因组复制部分的拷贝数加倍。在细菌和古细菌中，基因表达随基因剂量而变化，两者都在DNA复制后增加。Voichek等人，然而，这表明复制后DNA剂量增加不会增加芽殖酵母中的基因表达。这种表达缓冲由沉积在复制DNA上的新合成的组蛋白H3的乙酰化介导。这种乙酰化有助于抑制过量DNA的转录。由DNA复制驱动的基因剂量效应引起的潜在基因表达变化被组蛋白乙酰化缓冲。基因组复制引入了可用于转录的DNA模板的逐步增加。在S期早期复制的基因在晚期复制基因之前经历这种增加，这提出了DNA复制如何影响表达水平的问题。我们发现，在芽殖酵母中，信使RNA（mRNA）的合成速率对S期基因剂量的变化进行缓冲。这种表达稳态依赖于H3在其内部K56位点被Rtt 109/Asf 1乙酰化。删除这些因子，突变H3 K56或上调其去乙酰化，增加S期的基因表达，与基因复制时间成比例。因此，新沉积的组蛋白上的H3 K56乙酰化降低了复制DNA的转录效率，补充了其在保护基因组稳定性中的作用。我们的研究为DNA复制过程中维持表达稳态的机制提供了分子视角。
Doubling DNA but not expression As the genome replicates, and before the cell divides, the copy number of the replicated portions of the genome doubles. In bacteria and archaea, gene expression tracks with gene dosage, both of which increase after DNA replication. Voichek et al., however, show that an increase in DNA dosage after replication does not increase gene expression in budding yeast. This expression buffering is mediated by the acetylation of newly synthesized histone H3 deposited on the replicated DNA. This acetylation helps suppress transcription from the excess DNA. Science, this issue p. 1087 Potential gene expression changes caused by DNA replication–driven gene dosage effects are buffered by histone acetylation. Genome replication introduces a stepwise increase in the DNA template available for transcription. Genes replicated early in S phase experience this increase before late-replicating genes, raising the question of how expression levels are affected by DNA replication. We show that in budding yeast, messenger RNA (mRNA) synthesis rate is buffered against changes in gene dosage during S phase. This expression homeostasis depends on acetylation of H3 on its internal K56 site by Rtt109/Asf1. Deleting these factors, mutating H3K56 or up-regulating its deacetylation, increases gene expression in S phase in proportion to gene replication timing. Therefore, H3K56 acetylation on newly deposited histones reduces transcription efficiency from replicated DNA, complementing its role in guarding genome stability. Our study provides molecular insight into the mechanism maintaining expression homeostasis during DNA replication.