Fission yeast chromatin assembly factor 1 assists in the replication-coupled maintenance of heterochromatin
Fission yeast chromatin assembly factor 1 assists in the replication-coupled maintenance of heterochromatin
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DOI：
10.1111/j.1365-2443.2008.01225.x
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发表时间：
2008-10-01
期刊：
影响因子：
2.1
通讯作者：
Murakami, Yota
中科院分区：
文献类型：
--
作者：
Dohke, Kohei;Miyazaki, Shota;Murakami, Yota
染色质组装因子-1（Chromatin assembly factor-1，CAF 1）是一种高度保守的组蛋白分子伴侣，它通过与复制因子PCNA的相互作用，将组蛋白H3-H4复合物装载到体外新合成的DNA上。CAF 1被认为参与了几种生物体中异染色质的维持，但证据是间接的，功能细节尚未确定。我们鉴定了裂殖酵母CAF-1（spCAF 1），其在S期与PCNA相互作用。耗尽spCAF 1引起的缺陷沉默在着丝粒和交配位点异染色质，伴随着减少Swi 6，分裂酵母HP 1同源。spCAF 1的丢失使亚稳定异染色质区的染色质的沉默和活性状态都不稳定，对沉默状态的影响更明显，表明spCAF 1参与了异染色质的维持。Swi 6在G1/S期从异染色质中解离，似乎与spCAF 1相关。在早期S期，spCAF 1定位于复制异染色质以及常染色质，并保持与Swi 6，然后Swi 6结合到异染色质。两者合计，我们建议，spCAF 1的功能在异染色质的维护招聘错位Swi 6在复制过程中复制异染色质在复制叉。
Chromatin assembly factor-1 (CAF1) is a well-conserved histone chaperone that loads the histone H3-H4 complex onto newly synthesized DNA in vitro through interaction with the replication factor PCNA. CAF1 is considered to be involved in heterochromatin maintenance in several organisms, but the evidence is circumstantial and functional details have not been established. We identified fission yeast CAF-1 (spCAF1), which interacts with PCNA in S phase. Depletion of spCAF1 caused defects in silencing at centromeric and mating locus heterochromatin, accompanied with a decrease in Swi6, the fission yeast HP1 homologue. Loss of spCAF1 destabilized both the silent and active states of chromatin at the meta-stable heterochromatic region, with a more pronounced effect on the silent state, indicating that spCAF1 is involved in the maintenance of heterochromatin. Swi6 dissociated from heterochromatin during G1/S phase appears to associate with spCAF1. In early S phase, spCAF1 localized to replicating heterochromatin as well as euchromatin and remained associated with Swi6, and Swi6 then bound to heterochromatin. Taken together, we propose that spCAF1 functions in heterochromatin maintenance by recruiting dislocated Swi6 during replication to replicated heterochromatin at the replication fork.