A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast.
A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast.
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DOI：
10.1186/s13059-014-0481-4
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发表时间：
2014
期刊：
影响因子：
12.3
通讯作者：
Allshire RC
中科院分区：
文献类型：
--
作者：
Bayne EH;Bijos DA;White SA;de Lima Alves F;Rappsilber J;Allshire RC
异染色质在真核生物基因组的调控和稳定中起着重要作用。异染色质组分和促进异染色质组装的途径，包括RNA干扰，RNAi，在裂殖酵母裂殖酵母和人类之间广泛保守。因此，裂殖酵母已成为解剖异染色质完整性机制的重要模型系统。到目前为止，已经发现超过50种蛋白质有助于异染色质组装在裂殖酵母着丝粒。然而，以前的研究并不是详尽无遗的，因此可能还有更多的因素有待确定。为了更全面地了解异染色质组装途径，我们对着丝粒异染色质完整性所需的因素进行了系统的遗传筛选。除了已知的RNAi和染色质修饰成分外，我们还鉴定了几种在异染色质调节中具有先前未描述的作用的蛋白质。这些包括已知的和新表征的剪接相关蛋白，其是通过RNAi途径正确处理着丝粒转录物所必需的，以及COP 9信号体组分Csn1和Csn2，其在异染色质组装中的作用至少部分可以通过异染色质调节剂Epe 1的Ddb1依赖性降解中的作用来解释。这项工作揭示了参与分裂酵母中RNAi指导的异染色质组装的新因素。我们的研究结果支持并扩展了先前的观察结果，即剪接机制的组成部分是RNAi的平台，并证明了COP9信号体在异染色质调控中的新作用。本文的在线版本（doi：10.1186/s13059 - 014 - 0481 - 4）包含补充材料，可供授权用户使用。
Heterochromatin plays important roles in the regulation and stability of eukaryotic genomes. Both heterochromatin components and pathways that promote heterochromatin assembly, including RNA interference, RNAi, are broadly conserved between the fission yeast Schizosaccharomyces pombe and humans. As a result, fission yeast has emerged as an important model system for dissecting mechanisms governing heterochromatin integrity. Thus far, over 50 proteins have been found to contribute to heterochromatin assembly at fission yeast centromeres. However, previous studies have not been exhaustive, and it is therefore likely that further factors remain to be identified. To gain a more complete understanding of heterochromatin assembly pathways, we have performed a systematic genetic screen for factors required for centromeric heterochromatin integrity. In addition to known RNAi and chromatin modification components, we identified several proteins with previously undescribed roles in heterochromatin regulation. These included both known and newly characterised splicing-associated proteins, which are required for proper processing of centromeric transcripts by the RNAi pathway, and COP9 signalosome components Csn1 and Csn2, whose role in heterochromatin assembly can be explained at least in part by a role in the Ddb1-dependent degradation of the heterochromatin regulator Epe1. This work has revealed new factors involved in RNAi-directed heterochromatin assembly in fission yeast. Our findings support and extend previous observations that implicate components of the splicing machinery as a platform for RNAi, and demonstrate a novel role for the COP9 signalosome in heterochromatin regulation. The online version of this article (doi:10.1186/s13059-014-0481-4) contains supplementary material, which is available to authorized users.
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影响因子：
4.5
作者：
Buscaino A;White SA;Houston DR;Lejeune E;Simmer F;de Lima Alves F;Diyora PT;Urano T;Bayne EH;Rappsilber J;Allshire RC
通讯作者：
Allshire RC
影响因子：
4.5
作者：
Huang CF;Miki D;Tang K;Zhou HR;Zheng Z;Chen W;Ma ZY;Yang L;Zhang H;Liu R;He XJ;Zhu JK
通讯作者：
Zhu JK
DOI：
10.1038/nrg3355
发表时间：
2013-02
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0606536103
发表时间：
2006-10-10
影响因子：
11.1
作者：
Herr, Alan J.;Molnar, Attila;Baulcombe, David C.
通讯作者：
Baulcombe, David C.
影响因子：
11.4
作者：
Buscaino, Alessia;Lejeune, Erwan;Allshire, Robin C.
通讯作者：
Allshire, Robin C.