Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.

Forkhead transcription factors establish origin timing and long-range clustering in S. cerevisiae.
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DOI:
10.1016/j.cell.2011.12.012
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发表时间:
2012-01-20
期刊:
影响因子:
64.5
通讯作者:
Aparicio OM
Aparicio OM
中科院分区:
生物学1区
文献类型:
--
作者:
Knott SR;Peace JM;Ostrow AZ;Gan Y;Rex AE;Viggiani CJ;Tavaré S;Aparicio OM

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真核生物染色体的复制是通过复制起点功能的表观遗传调控在细胞核内进行时空组织的。特定起源的特征性起始时间被认为反映了它们的染色质环境或亚核定位,然而其机制仍然不清楚。在这里,我们表明,酵母叉头转录因子,Fkh 1和Fkh 2,是全球性的决定因素的复制起点的时间。叉头调控的起源时间是独立的本地水平或转录的变化。相反,我们表明,Fkh 1和Fkh 2所需的早期起源的集群和他们的协会与关键起始因子Cdc 45在G1期,这表明Fkh 1和Fkh 2选择性地招募起源到紧急复制工厂。Fkh 1和Fkh 2结合Fkh-activated起源,并与ORC物理相互作用,为聚类起源提供了一个合理的机制。这些发现增加了一个新的层面,我们的理解的表观遗传基础的差异起源调节及其连接到染色体结构域组织。
The replication of eukaryotic chromosomes is organized temporally and spatially within the nucleus through epigenetic regulation of replication origin function. The characteristic initiation timing of specific origins is thought to reflect their chromatin environment or sub-nuclear positioning, however the mechanism remains obscure. Here we show that the yeast Forkhead transcription factors, Fkh1 and Fkh2, are global determinants of replication origin timing. Forkhead regulation of origin timing is independent of local levels or changes of transcription. Instead, we show that Fkh1 and Fkh2 are required for the clustering of early origins and their association with the key initiation factor Cdc45 in G1-phase, suggesting that Fkh1 and Fkh2 selectively recruit origins to emergent replication factories. Fkh1 and Fkh2 bind Fkh-activated origins, and interact physically with ORC, providing a plausible mechanism to cluster origins. These findings add a new dimension to our understanding of the epigenetic basis for differential origin regulation and its connection to chromosomal domain organization.
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