DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.
DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.
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DOI：
10.1038/s41467-018-06624-0
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发表时间：
2018-10-23
影响因子：
16.6
通讯作者：
Riedel CG
中科院分区：
文献类型：
--
作者：
Lin XX;Sen I;Janssens GE;Zhou X;Fonslow BR;Edgar D;Stroustrup N;Swoboda P;Yates JR 3rd;Ruvkun G;Riedel CG
感知和应对有害条件的能力对任何生物的生存至关重要。转录因子fos-16/FOXO是这些反应的核心，将痛苦信号传递到抗应激和长寿促进基因的表达中。然而，它是否足以完成这项复杂的任务仍不清楚。利用C. elegans，我们表明，ESTA-16不单独发挥作用，但作为一个转录调控模块的一部分，与转录因子HLH-30/TFEB一起。在有害条件下，两种转录因子都易位到细胞核中，在那里它们通常形成复合物，共同占据靶启动子，并共同调节许多靶基因。有趣的是，它们的协同作用是刺激依赖的：它们相互依赖，在相同的途径中发挥作用，以促进长寿或抗氧化应激，但它们独立地引起热应激反应，甚至在dauer形成过程中相互对抗。我们提出，这个模块的ESTA-16和HLH-30的行为，通过组合基因调控传递遇险信号到特定的目标基因集的表达，确保最佳的生存在每一个给定的威胁。转录因子fos-16/FOXO是胰岛素/胰岛素样生长因子信号转导的下游效应子，在抗应激和长寿中起重要作用。在这里，作者表明，HLH-16/FOXO可以与HLH-30/TFEB形成复合物，协同调节靶基因的转录，以响应某些应激刺激。
The ability to perceive and respond to harmful conditions is crucial for the survival of any organism. The transcription factor DAF-16/FOXO is central to these responses, relaying distress signals into the expression of stress resistance and longevity promoting genes. However, its sufficiency in fulfilling this complex task has remained unclear. Using C. elegans, we show that DAF-16 does not function alone but as part of a transcriptional regulatory module, together with the transcription factor HLH-30/TFEB. Under harmful conditions, both transcription factors translocate into the nucleus, where they often form a complex, co-occupy target promoters, and co-regulate many target genes. Interestingly though, their synergy is stimulus-dependent: They rely on each other, functioning in the same pathway, to promote longevity or resistance to oxidative stress, but they elicit heat stress responses independently, and they even oppose each other during dauer formation. We propose that this module of DAF-16 and HLH-30 acts by combinatorial gene regulation to relay distress signals into the expression of specific target gene sets, ensuring optimal survival under each given threat. The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
10.5
作者：
Hamilton, B;Doug, YQ;Lee, SS
通讯作者：
Lee, SS
影响因子：
7.8
作者：
Park SK;Tedesco PM;Johnson TE
通讯作者：
Johnson TE
影响因子：
29
作者：
Heimbucher T;Liu Z;Bossard C;McCloskey R;Carrano AC;Riedel CG;Tanasa B;Klammt C;Fonslow BR;Riera CE;Lillemeier BF;Kemphues K;Yates JR 3rd;O'Shea C;Hunter T;Dillin A
通讯作者：
Dillin A