Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1
Maintenance of Silent Chromatin through Replication Requires SWI/SNF-like Chromatin Remodeler SMARCAD1
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DOI：
10.1016/j.molcel.2011.02.036
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发表时间：
2011-05-06
期刊：
影响因子：
16
通讯作者：
Mermoud, Jacqueline E.
中科院分区：
文献类型：
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作者：
Rowbotham, Samuel P.;Barki, Leila;Mermoud, Jacqueline E.
表观遗传标记，如翻译后组蛋白修饰，指定了潜在DNA序列的功能状态，尽管它们在DNA复制过程中被破坏后如何维持仍然是一个关键问题。我们发现哺乳动物SWI/ snf样蛋白SMARCAD1是重建抑制性染色质所需的关键因子。SMARCAD1的atp酶活性对于组蛋白H3/H4的全局去乙酰化是必需的。通过这种方式，SMARCAD1促进H3K9的甲基化、异染色质的建立和忠实的染色体分离。SMARCAD1与转录抑制因子KAP1、组蛋白去乙酰化酶HDAC1/2和组蛋白甲基转移酶G9a/GLP相关，并调节HDAC1和KAP1与异染色质的相互作用。SMARCAD1直接与复制机制的核心组件PCNA相互作用，并被招募到DNA复制位点。我们的研究结果表明，SMARCAD1的染色质重塑确保了沉默的位点，如中心外异染色质，被正确地延续。
Epigenetic marks such as posttranslational histone modifications specify the functional states of underlying DNA sequences, though how they are maintained after their disruption during DNA replication remains a critical question. We identify the mammalian SWI/SNF-like protein SMARCAD1 as a key factor required for the re-establishment of repressive chromatin. The ATPase activity of SMARCAD1 is necessary for global deacetylation of histones H3/H4. In this way, SMARCAD1 promotes methylation of H3K9, the establishment of heterochromatin, and faithful chromosome segregation. SMARCAD1 associates with transcriptional repressors including KAP1, histone deacetylases HDAC1/2 and the histone methyltransferase G9a/GLP and modulates the interaction of HDAC1 and KAP1 with heterochromatin. SMARCAD1 directly interacts with PCNA, a central component of the replication machinery, and is recruited to sites of DNA replication. Our findings suggest that chromatin remodeling by SMARCAD1 ensures that silenced loci, such as pericentric heterochromatin, are correctly perpetuated.