Université de Grenoble Alpes (UGA), 38700 La Tronche, France.
Institute for Advanced Biosciences (IAB), Centre de Recherche UGA/Inserm U 1209/CNRS UMR 5309, Site Santé-Allée des Alpes, 38700 La Tronche, France.
Genes (Basel). 2022 Mar 27;13(4):597. doi: 10.3390/genes13040597.
In eukaryotes, the heat shock response is orchestrated by a transcription factor named Heat Shock Factor 1 (HSF1). HSF1 is mostly characterized for its role in activating the expression of a repertoire of protein-coding genes, including the heat shock protein (HSP) genes. Remarkably, a growing set of reports indicate that, upon heat shock, HSF1 also targets various non-coding regions of the genome. Focusing primarily on mammals, this review aims at reporting the identity of the non-coding genomic sites directly bound by HSF1, and at describing the molecular function of the long non-coding RNAs (lncRNAs) produced in response to HSF1 binding. The described non-coding genomic targets of HSF1 are pericentric Satellite DNA repeats, (sub)telomeric DNA repeats, Short Interspersed Nuclear Element (SINE) repeats, transcriptionally active enhancers and the NEAT1 gene. This diverse set of non-coding genomic sites, which already appears to be an integral part of the cellular response to stress, may only represent the first of many. Thus, the study of the evolutionary conserved heat stress response has the potential to emerge as a powerful cellular context to study lncRNAs, produced from repeated or unique DNA regions, with a regulatory function that is often well-documented but a mode of action that remains largely unknown.
在真核生物中,热休克反应是由一种名为热休克因子 1(HSF1)的转录因子协调的。HSF1 的主要特征是其在激活一系列蛋白质编码基因(包括热休克蛋白(HSP)基因)表达中的作用。值得注意的是,越来越多的报告表明,在热休克后,HSF1 还靶向基因组的各种非编码区域。本综述主要针对哺乳动物,旨在报告 HSF1 直接结合的非编码基因组位点的身份,并描述响应 HSF1 结合产生的长非编码 RNA(lncRNA)的分子功能。描述的 HSF1 非编码基因组靶标是着丝粒卫星 DNA 重复序列、(亚)端粒 DNA 重复序列、短散布核元件(SINE)重复序列、转录活性增强子和 NEAT1 基因。这一组多样化的非编码基因组位点似乎已经成为细胞应激反应的一个组成部分,但可能只是众多非编码基因组位点中的第一批。因此,对进化上保守的热应激反应的研究有可能成为研究 lncRNA 的强大细胞背景,lncRNA 来自重复或独特的 DNA 区域,具有经常有充分记录的调节功能,但作用模式在很大程度上仍是未知的。