Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner
Orc5 induces large-scale chromatin decondensation in a GCN5-dependent manner
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DOI：
10.1242/jcs.178889
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发表时间：
2016-01-15
影响因子：
4
通讯作者：
Prasanth, Supriya G.
中科院分区：
文献类型：
--
作者：
Giri, Sumanprava;Chakraborty, Arindam;Prasanth, Supriya G.
在真核生物中，起源识别复合物 (ORC) 蛋白在起源处建立复制前复合物 (preRC)，这对于 DNA 复制的启动至关重要。开放染色质结构调节 preRC 形成和复制起始的效率。然而，控制染色质结构的分子机制以及 preRC 成分如何在染色质上建立仍有待了解。在人类细胞中，ORC 是一个高度动态的复合体，具有许多独立的功能，这些功能归因于 ORC 的子复合体或单个亚基，包括异染色质组织、端粒和着丝粒功能、中心体复制和胞质分裂。我们证明，与其他 ORC 亚基不同，人类 Orc5 当异位连接到染色质位点时，会诱导大规模染色质解浓缩，主要是在细胞周期的 G1 期。 Orc5 与 H3 组蛋白乙酰转移酶 GCN5（也称为 KAT2A）结合，这种结合增强了 Orc5 的染色质打开功能。在缺少 Orc5 的情况下，组蛋白 H3 乙酰化在起始点就会降低。我们认为 Orc5 在 G1 期间诱导染色质展开的能力允许在起点建立 preRC。
In eukaryotes, origin recognition complex (ORC) proteins establish the pre-replicative complex (preRC) at the origins, and this is essential for the initiation of DNA replication. Open chromatin structures regulate the efficiency of preRC formation and replication initiation. However, the molecular mechanisms that control chromatin structure, and how the preRC components establish themselves on the chromatin remain to be understood. In human cells, the ORC is a highly dynamic complex with many separate functions attributed to sub-complexes or individual subunits of the ORC, including heterochromatin organization, telomere and centromere function, centrosome duplication and cytokinesis. We demonstrate that human Orc5, unlike other ORC subunits, when ectopically tethered to a chromatin locus, induces large-scale chromatin decondensation, predominantly during G1 phase of the cell cycle. Orc5 associates with the H3 histone acetyl transferase GCN5 (also known as KAT2A), and this association enhances the chromatin-opening function of Orc5. In the absence of Orc5, histone H3 acetylation is decreased at the origins. We propose that the ability of Orc5 to induce chromatin unfolding during G1 allows the establishment of the preRC at the origins.