Drosophila GAGA factor polyglutamine domains exhibit prion-like behavior.
Drosophila GAGA factor polyglutamine domains exhibit prion-like behavior.
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DOI：
10.1186/1471-2164-14-374
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发表时间：
2013-06-03
期刊：
影响因子：
4.4
通讯作者：
Paro R
中科院分区：
文献类型：
--
作者：
Tariq M;Wegrzyn R;Anwar S;Bukau B;Paro R
果蝇GAGA因子（GAF）参与核小体重塑以激活基因，作为抗抑制因子并与异染色质相关，有助于基因抑制。GAF功能与基于染色质的表观遗传控制密切相关，将基本转录调控与基因表达的可遗传长期维持联系起来。这些不同的功能需要GAF在不同的多蛋白复合物中与不同的伙伴相互作用。GAF的两种异构体描述了高度保守的富含谷氨酰胺的c端结构域（Q结构域），这与复合物的形成有关。我们发现Q结构域具有类似朊病毒的性质。在一个已建立的酵母测试系统中，两个GAF Q结构域传递的朊病毒活性与已知的酵母朊病毒相当。Q结构域稳定地保持两种不同的构象状态，对融合酵母报告蛋白施加功能限制。在胍HCl存在下或通过过度表达Hsp104伴侣蛋白，可以可逆地治愈朊病毒样表型。此外，当与GFP融合时，Q结构域在酵母细胞中形成聚集体。我们的结论是，GAF Q结构域的类似朊病毒的行为表明，这种c端结构可能执行稳定的构象转换。这种自我延续的构象变化可以帮助GAF在果蝇中执行其基因控制的多种表观遗传功能。
The Drosophila GAGA factor (GAF) participates in nucleosome remodeling to activate genes, acts as an antirepressor and is associated with heterochromatin, contributing to gene repression. GAF functions are intimately associated to chromatin-based epigenetic control, linking basic transcriptional regulation to heritable long-term maintenance of gene expression. These diverse functions require GAF to interact with different partners in different multiprotein complexes. The two isoforms of GAF depict highly conserved glutamine-rich C-terminal domains (Q domain), which have been implicated in complex formation. Here we show that the Q domains exhibit prion-like properties. In an established yeast test system the two GAF Q domains convey prion activities comparable to well known yeast prions. The Q domains stably maintain two distinct conformational states imposing functional constraints on the fused yeast reporter protein. The prion-like phenotype can be reversibly cured in the presence of guanidine HCl or by over-expression of the Hsp104 chaperone protein. Additionally, when fused to GFP, the Q domains form aggregates in yeast cells. We conclude that prion-like behavior of the GAF Q domain suggests that this C-terminal structure may perform stable conformational switches. Such a self-perpetuating change in the conformation could assist GAF executing its diverse epigenetic functions of gene control in Drosophila.
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影响因子：
56.9
作者：
MASISON, DC;WICKNER, RB
通讯作者：
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