SNF2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance and Proper Replication.
SNF2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance and Proper Replication.
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DOI：
10.1016/j.molcel.2017.02.006
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发表时间：
2017-04-06
期刊：
影响因子：
16
通讯作者：
Grewal SI
中科院分区：
文献类型：
--
作者：
Taneja N;Zofall M;Balachandran V;Thillainadesan G;Sugiyama T;Wheeler D;Zhou M;Grewal SI
异染色质可以在顺式基因中表观遗传，导致稳定的基因沉默。然而，异染色质遗传的机制仍不清楚。在这里，我们发现Fft3，一种哺乳动物SMARCAD1SNF2染色质重塑的分裂酵母同源物，是异染色质遗传所必需的因子，而不是重新组装所需的因子。重要的是，我们发现Fft3抑制了异染色质基因座上组蛋白的周转，从而促进了异染色质在循环细胞中的表观遗传传递。此外，Fft3还阻止了几个常染点上的核小体翻转，以防止R环的形成，确保适当的复制过程。我们的分析表明，CLR4/Suv39h的过表达也是通过这些座位进行有效复制所必需的，它抑制了与Fft3丢失相关的表型。这项工作揭示了一个对异染色质表观遗传至关重要的保守因子，并描述了一种机制，即抑制核小体周转防止形成阻碍基因组脆弱区域复制的结构障碍。Taneja等人。结果表明，SNF2家族染色质重构体抑制组蛋白周转以促进异染色质在分裂细胞中的表观遗传传递，并揭示了在特定基因组位置抑制核小体周转促进适当复制的机制
Heterochromatin can be epigenetically inherited in cis, leading to stable gene silencing. However, the mechanisms underlying heterochromatin inheritance remain unclear. Here we identify Fft3, a fission yeast homolog of the mammalian SMARCAD1 SNF2 chromatin remodeler, as a factor uniquely required for heterochromatin inheritance, rather than for de novo assembly. Importantly, we find that Fft3 suppresses turnover of histones at heterochromatic loci to facilitate epigenetic transmission of heterochromatin in cycling cells. Moreover, Fft3 also precludes nucleosome turnover at several euchromatic loci to prevent R-loop formation, ensuring proper replication progression. Our analyses show that overexpression of Clr4/Suv39h, which is also required for efficient replication through these loci, suppresses phenotypes associated with the loss of Fft3. This work uncovers a conserved factor critical for epigenetic inheritance of heterochromatin, and describes a mechanism in which suppression of nucleosome turnover prevents formation of structural barriers that impede replication at fragile regions in the genome. Taneja et al. show that a SNF2 family chromatin remodeler suppresses histone turnover to promote epigenetic transmission of heterochromatin in dividing cells, and uncover a mechanism in which suppression of nucleosome turnover at specific genomic sites facilitates proper replication