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首页> 外文期刊>Molecular and Cellular Biology >Fidelity of Histone Gene Regulation Is Obligatory for Genome Replication and Stability
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Fidelity of Histone Gene Regulation Is Obligatory for Genome Replication and Stability

机译：组蛋白基因调节的保真度对于基因组复制和稳定性是必不可少的

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Fidelity of chromatin organization is crucial for normal cell cycle progression, and perturbations in packaging of DNA may predispose to transformation. Histone H4 protein is the most highly conserved chromatin protein, required for nucleosome assembly, with multiple histone H4 gene copies encoding identical protein. There is a long-standing recognition of the linkage of histone gene expression and DNA replication. A fundamental and unresolved question is the mechanism that couples histone biosynthesis with DNA replication and fidelity of cell cycle control. Here, we conditionally ablated the obligatory histone H4 transcription factor HINFP to cause depletion of histone H4 in mammalian cells. Deregulation of histone H4 results in catastrophic cellular and molecular defects that lead to genomic instability. Histone H4 depletion increases nucleosome spacing, impedes DNA synthesis, alters chromosome complement, and creates replicative stress. Our study provides functional evidence that the tight coupling between DNA replication and histone synthesis is reciprocal.
机译：染色质组织的保真度对于正常的细胞周期进程至关重要，而DNA包装中的干扰可能易于转化。组蛋白H4蛋白是核糖体组装所需的最高度保守的染色质蛋白，具有多个编码相同蛋白的组蛋白H4基因拷贝。对组蛋白基因表达和DNA复制之间的联系有着长期的认识。一个根本未解决的问题是将组蛋白生物合成与DNA复制和细胞周期控制保真性结合的机制。在这里，我们有条件地消融了必需的组蛋白H4转录因子HINFP，以导致哺乳动物细胞中组蛋白H4的消耗。组蛋白H4的失调会导致灾难性的细胞和分子缺陷，从而导致基因组不稳定。组蛋白H4消耗增加了核小体的间隔，阻碍了DNA的合成，改变了染色体的互补性，并产生了复制压力。我们的研究提供了功能性证​​据，证明DNA复制与组蛋白合成之间的紧密结合是相互的。

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