HEAT-INDUCED TRANSCRIPTION FROM RNA POLYMERASE-II AND POLYMERASE-III AND HSF BINDING-ACTIVITY ARE COORDINATELY REGULATED BY THE PRODUCTS OF THE HEAT-SHOCK GENES

Heat shock leads to co-ordinate increases in transcription of a family of heat shock genes, including the mouse hsp70.1 and B2 genes. Activation of the heat shock transcription factor (HSF) by heat shock stimulates transcription of the murine hsp70.1 gene (by RNA polymerase II). B2 genes are short, repetitive sequences whose transcription (by RNA polymerase III) are also increased after heat shock. We have studied whether heat-induced transcription is auto-regulated by the products of the heat shock genes. The results indicate: (1) after an initial heat shock, transcription of the heat shock genes by RNA polymerases II and III becomes desensitized to further heat shock, and the heat-induced DNA binding activity of the HSF is lost, (2) if accumulation of heat shock gene products is inhibited, the desensitizing effect of a prior heat shock is removed, and (3) transcription of the hsp70.1 and B2 genes apparently involves different mechanisms, with hsp70.1 employing the HSF and the B2 gene using a separate, heat-activated transcriptional mechanism. However, the level of transcription from the hsp70.1 and B2 genes and the stability of their respective RNAs are co-ordinately regulated by the level of heat shock protein in the cell. The data indicate that auto-regulation of the level of mouse heat shock gene products is mediated by RNA polymerase II transcripts but that the regulatory mechanism can control transcription from RNA polymerase III genes as well.