复制时间维持着人类细胞的全局表观遗传状态。
Replication timing maintains the global epigenetic state in human cells.
机构信息
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
出版信息
Science. 2021 Apr 23;372(6540):371-378. doi: 10.1126/science.aba5545. Epub 2021 Apr 22.
Abstract
The temporal order of DNA replication [replication timing (RT)] is correlated with chromatin modifications and three-dimensional genome architecture; however, causal links have not been established, largely because of an inability to manipulate the global RT program. We show that loss of RIF1 causes near-complete elimination of the RT program by increasing heterogeneity between individual cells. RT changes are coupled with widespread alterations in chromatin modifications and genome compartmentalization. Conditional depletion of RIF1 causes replication-dependent disruption of histone modifications and alterations in genome architecture. These effects were magnified with successive cycles of altered RT. These results support models in which the timing of chromatin replication and thus assembly plays a key role in maintaining the global epigenetic state.
摘要
DNA 复制的时间顺序[复制时间（RT）]与染色质修饰和三维基因组结构相关；然而，由于无法操纵全局 RT 程序，因此尚未建立因果关系。我们表明，RIF1 的缺失通过增加单个细胞之间的异质性，几乎完全消除了 RT 程序。RT 变化与染色质修饰和基因组区室化的广泛改变相关。RIF1 的条件性耗竭导致复制依赖性组蛋白修饰的破坏和基因组结构的改变。随着 RT 改变的连续循环，这些影响被放大。这些结果支持这样的模型，即染色质复制的时间顺序以及因此的组装在维持全局表观遗传状态中起着关键作用。
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