The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress
The loop domain of heat shock transcription factor 1 dictates DNA-binding specificity and responses to heat stress
复制标题
DOI：
10.1101/gad.894801
复制
发表时间：
2001-08-15
影响因子：
10.5
通讯作者：
Thiele, DJ
中科院分区：
文献类型：
--
作者：
Ahn, SG;Liu, PCC;Thiele, DJ
真核生物热休克转录因子（HSF）调控着一条进化上保守的应激反应途径，对抵御各种环境和发育应激至关重要。尽管高度相似的HSF家族成员在应对压力和激活靶基因表达方面具有不同的作用，但控制这些作用的机制尚不清楚。在这里，我们在HSF1 DNA结合域中发现了一个环，该环在体外指示HSF异构体特异性DNA结合，并在酵母转录试验和哺乳动物细胞中指示HSF家族成员优先激活靶基因。HSF1环区的这些特征可转座到HSF2，足以赋予dna结合特异性，热休克诱导的HSP基因表达和保护热诱导的细胞凋亡。此外，该环在基础条件下抑制HSF1三聚体的形成，并且是体外纯化系统中热诱导三聚体化所必需的，这表明该结构域是HSF1热应力传感机制的关键部分。我们认为，这个结构域定义了HSF1的一个特征，它构成了细胞如何利用转录因子家族来响应不同应激的重要决定因素。
Eukaryotic heat shock transcription factors (HSF) regulate an evolutionarily conserved stress-response pathway essential for survival against a variety of environmental and developmental stresses. Although the highly similar HSF family members have distinct roles in responding to stress and activating target gene expression, the mechanisms that govern these roles are unknown. Here we identify a loop within the HSF1 DNA-binding domain that dictates HSF isoform specific DNA binding in vitro and preferential target gene activation by HSF family members in both a yeast transcription assay and in mammalian cells. These characteristics of the HSF1 loop region are transposable to HSF2 and sufficient to confer DNA-binding specificity, heat shock inducible HSP gene expression and protection from heat-induced apoptosis in vivo. In addition, the loop suppresses formation of the HSF1 trimer under basal conditions and is required for heat-inducible trimerization in a purified system in vitro, suggesting that this domain is a critical part of the HSF1 heat-stress-sensing mechanism. We propose that this domain defines a signature for HSF1 that constitutes an important determinant for how cells utilize a family of transcription factors to respond to distinct stresses.