A Mass Action Model for Heat Shock Induced Enhancer Transcription

A proper response to elevated temperature is important for the survival of all organisms. This response is partially achieved through enhancer-mediated regulation of gene expression. However, the behavior of enhancers during heat shock response is not well understood. Here, we report that binding by heat shock factor 1 (HSF1), the master regulator of heat shock response, leads to upregulation of enhancer transcription. HSF1 bound enhancers also show higher-than-expected probability to be near heat induced genes, indicating their potential involvement in the upregulation of these genes. However, the transcriptional upregulation of the majority of enhancers during heat shock is HSF1 independent. To account for this observation, we propose a mass action model of enhancer transcription. Heat shock response results in a global downregulation of gene transcription, which leads to less transcribing RNA polymerase II (Pol II) and more freely diffusing Pol II. Free Pol II can then initiate transcription on accessible chromatin regions driven by the law of mass action.