Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae
Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae
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新发现的朊病毒与酿酒酵母中染色质重塑因子 Swi1 相关
DOI：
10.1038/ng.112
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发表时间：
2008-04-01
期刊：
影响因子：
30.8
通讯作者：
Li, Liming
中科院分区：
文献类型：
--
作者：
Du, Zhiqiang;Park, Kyung-Won;Li, Liming
SWI/SNF是一种进化上保守的依赖于ATP的染色质重塑复合体，在转录调控中发挥着重要作用。在酿酒酵母中，SWI/SNF通过激活或抑制调控大约6%的基因的表达(2)。Swi1是SWI/SNF的一个亚基，含有一个富含谷氨酰胺和天冬酰胺的N-末端区域，这是所有特征酵母蛋白的一个显著特征--一组能够在构象和功能上自我持续变化的独特蛋白质[3]。在这里，我们提供了Swi1可以成为Prion的证据，[SWI+]。Swi1聚集在[SWI+]细胞中，但不聚集在非蛋白细胞中。携带[SWI+]的细胞表现出部分功能丧失的SWI/SNF表型。[Swi+]可通过盐酸胍处理、Hsp104缺失或Swi1缺失来消除。此外，我们发现[SWI+]主要通过细胞质传递。我们的发现揭示了一种“纯蛋白质”遗传的新机制，该机制导致染色质重塑的修改，并最终导致全球基因调控。
SWI/SNF, an evolutionarily conserved ATP-dependent chromatin-remodeling complex, has an important role in transcriptional regulation(1). In Saccharomyces cerevisiae, SWI/SNF regulates the expression of similar to 6% of total genes through activation or repression(2). Swi1, a subunit of SWI/SNF, contains an N-terminal region rich in glutamine and asparagine, a notable feature shared by all characterized yeast prions-a group of unique proteins capable of self-perpetuating changes in conformation and function(3). Here we provide evidence that Swi1 can become a prion, [SWI+]. Swi1 aggregates in [SWI+] cells but not in nonprion cells. Cells bearing [SWI+] show a partial loss-of-function phenotype of SWI/SNF. [SWI+] can be eliminated by guanidine hydrochloride treatment, HSP104 deletion or loss of Swi1. Moreover, we show [SWI+] is dominantly and cytoplasmically transmitted. Our findings reveal a novel mechanism of 'protein-only' inheritance that results in modification of chromatin-remodeling and, ultimately, global gene regulation.