Eriksson M, Jokinen E, Sistonen L, Leppä S
Haartman Institute, Department of Pathology, University of Helsinki, Finland.
Int J Dev Biol. 2000 Aug;44(5):471-7.
Two members of the heat shock transcription factor family, HSF1 and HSF2, have been identified as activators of mammalian heat shock gene expression. HSF1 acts as a classical stress-responsive factor, whereas HSF2 might play a role in embryogenesis, since it is active during pre- and post-implantation periods up to 15.5 days of mouse embryonic development. In this study, we analyzed HSF1 and HSF2 expression and activation during mouse heart formation. Our results show an abundant expression of HSF1 throughout heart development. In contrast, expression of the alternatively spliced HSF2-alpha and HSF2-beta, and an additional higher molecular weight isoform is strongly upregulated in the developing mouse heart at E11.5-12.5, a stage after which tubular heart has looped and chambers formed, and the myocardial walls are maturating and the valves differentiating. At the same developmental stage, HSF2 DNA-binding activity is transiently induced, whereas the weak HSE-binding activity, which is detected throughout heart development, consists primarily of HSF1. Interestingly, heat shock gene expression shows no temporal or spatial correlation with HSF2 expression and activation. Taken together, our results indicate that HSF2 activation is associated with specific stages of heart formation but is not involved in the regulation of inducible heat shock gene expression.
热休克转录因子家族的两个成员,即HSF1和HSF2,已被确定为哺乳动物热休克基因表达的激活因子。HSF1作为一种典型的应激反应因子,而HSF2可能在胚胎发生中发挥作用,因为它在小鼠胚胎发育的植入前和植入后阶段直至15.5天都是活跃的。在本研究中,我们分析了小鼠心脏形成过程中HSF1和HSF2的表达及激活情况。我们的结果显示HSF1在整个心脏发育过程中都有丰富的表达。相比之下,可变剪接的HSF2-α和HSF2-β以及另一种更高分子量的异构体在发育中的小鼠心脏中,于E11.5 - 12.5阶段(此时管状心脏已发生环化且腔室形成,心肌壁正在成熟且瓣膜正在分化)强烈上调。在同一发育阶段,HSF2的DNA结合活性被短暂诱导,而在整个心脏发育过程中检测到的微弱的热休克元件(HSE)结合活性主要由HSF1组成。有趣的是,热休克基因表达与HSF2的表达及激活没有时间或空间上的相关性。综上所述,我们的结果表明HSF2的激活与心脏形成的特定阶段相关,但不参与诱导性热休克基因表达的调控。