Developmentally dictated expression of heat shock factors:: Exclusive expression of HSF4 in the postnatal lens and its specific interaction with αB-crystallin heat shock promoter
Developmentally dictated expression of heat shock factors:: Exclusive expression of HSF4 in the postnatal lens and its specific interaction with αB-crystallin heat shock promoter
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DOI：
10.1074/jbc.m405813200
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发表时间：
2004-10-22
影响因子：
4.8
通讯作者：
Bhat, SP
中科院分区：
文献类型：
--
作者：
Somasundaram, T;Bhat, SP
在高等真核生物中，应激反应的分子级联反应开始于细胞质中热休克因子1的三聚化，随后它被转运到细胞核，在那里它与热休克元件结合，导致下游基因转录的激活(S)。这一成熟的范例主要是在培养细胞中进行的研究。热休克转录因子(HSFs)的发育和组织特异性调控及其与热休克启动子的相互作用尚不清楚。本文报道在大鼠晶状体中，在三种哺乳动物的HSFs中，HSF1和HSF2的表达主要是胎儿的，而HSF4的表达主要是出生后的。HSF1和HSF4在胎儿和成人晶状体中的表达模式相似。HSF1/2和HSF4的表达之间的这种阶段特异性的反向关系表明，组织特异性的应激管理取决于特定的HSF的存在或不存在(S)。除了实时聚合酶链式反应和免疫印迹，凝胶迁移率改变分析，结合来自三种不同热休克启动子的特异性抗体和HSE探针，证实在出生后晶状体核提取液中没有HSF1或HSF2结合活性。利用这个独特的体内发育调控系统，我们证明了1)HSF4与来自α-晶体蛋白、Hsp70和Hsp82启动子的热休克元件结合的特定模式，以及2)与α-晶体蛋白基因的典型热休克元件相互作用的是HSF4，而不是HSF1或HSF2。
The molecular cascade of stress response in higher eukaryotes commences in the cytoplasm with the trimerization of the heat shock factor 1 (HSF1), followed by its transport to the nucleus, where it binds to the heat shock element leading to the activation of transcription from the down-stream gene(s). This well-established paradigm has been mostly studied in cultured cells. The developmental and tissue-specific control of the heat shock transcription factors (HSFs) and their interactions with heat shock promoters remain unexplored. We report here that in the rat lens, among the three mammalian HSFs, expression of HSF1 and HSF2 is largely fetal, whereas the expression of HSF4 is predominantly postnatal. Similar pattern of expression of HSF1 and HSF4 is seen in fetal and adult human lenses. This stage-specific inverse relationship between the expression of HSF1/2 and HSF4 suggests tissue-specific management of stress depending on the presence or absence of specific HSF(s). In addition to real-time PCR and immunoblotting, gel mobility shift assays, coupled with specific antibodies and HSE probes, derived from three different heat shock promoters, establish that there is no HSF1 or HSF2 binding activity in the postnatal lens nuclear extracts. Using this unique, developmentally modulated in vivo system, we demonstrate 1) specific patterns of HSF4 binding to heat shock elements derived from alphaB-crystallin, Hsp70, and Hsp82 promoters and 2) that it is HSF4 and not HSF1 or HSF2 that interacts with the canonical heat shock element of the alphaB-crystallin gene.