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17 Modular Units of Heat Shock Regulatory Regions: Structure and Function

John T. Lis, Hua Xiao, Olga Perisic


Heat shock genes possess multiple copies of a sequence called the heat shock element (HSE) that is required for the stress-induced transcription of these genes. This element binds tightly to a regulatory protein called heat shock transcription factor (HSF). In this chapter, we summarize genetic and biochemical data that have led to the definition of both the DNA sequences required to create a heat-shock-inducible regulatory region and the interaction of these sequences with HSF. Also, we speculate on how the large complex of HSE/HSF may influence the frequency of transcription of heat shock genes.

Pelham (1982) and Mirault et al. (1982) reported the first functional analyses of the regulatory region of the Drosophila hsp70 gene by examining the expression of a series of deletion mutations that were transfected into monkey COS cells. Pelham showed that sequences between nucleotides −66 and −47 upstream of the hsp70 gene are necessary for heat-induced expression, and he identified a consensus CTGGAATTTCTAGA sequence (later simplified to the 14 bp sequence C--GAA--TTC--G) that is found upstream of all Drosophila heat shock genes. Regions upstream of a variety of heat shock genes in organisms as diverse as yeast and man possess sequences that match part or all of the HSE consensus (Nover 1987). The HSF protein, which binds to these sequences, has been purified from Drosophila, yeast, and human cells (Sorger and Pelham 1987; Wiederrecht et al. 1987; Wu et al. 1987; Goldenberg et al. 1988), and it stimulates transcription of heat...

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