18 Transcriptional Regulation of Heat Shock Genes

Abstract

I. INTRODUCTION
In all eukaryotes, transcriptional regulation of heat shock genes in response to elevated ambient temperatures is mediated by a common, positive, cis-acting sequence, the heat shock element (HSE), that is present in multiple copies upstream of the transcriptional start site. Originally defined as a 14-nucleotide sequence CT-GAA--TTC-AG (Pelham 1982), the HSE has recently been revised by further analysis to two or three modules consisting of alternating GAA or TTC blocks, arranged in alternating orientations and at 2-nucleotide intervals (Amin et al. 1988; Xiao and Lis 1988; see Lis et al., this volume). In this chapter, we focus on our current understanding of the transcriptional activator protein that stimulates the synthesis of heat shock mRNA through interaction with the HSE. Transcription factors that regulate some heat shock genes through cis elements that are unrelated to the HSE are not covered in this discussion.

Initial evidence for a factor that interacts with the HSE came from studies of protein/DNA interactions in Drosophila cell nuclei, in which a factor, heat shock activator protein, was found to bind specifically to the HSE only upon heat shock stimulation (Wu 1984a,b); parallel studies using DNA-binding and in vitro transcription assays also identified a heat shock transcription factor that bound specifically to the HSE (Parker and Topol 1984). At the 1987 Cold Spring Harbor Meeting entitled “The Role of Heat Shock and Stress Response in Biology and Human Disease,” HSE-binding factors were given a general designation: heat shock factor (HSF). In the following discussion,...