The anti-inflammatory drug sodium salicylate modulates the activity of
specific transcription factors in humans. Here we show that salicylat
e and sorbate, another organic acid, stimulate DNA binding by yeast he
at shock transcription factor (HSF) in vivo. Surprisingly, salicylate
inhibits heat shock gene transcription even in cells induced by a prio
r heat shock. This inhibition of transcription occurs at a step after
HSF and transcription factor IID binding but before promoter melting b
y RNA polymerase. Salicylate appears to generate a tight binding but a
ctivation-impotent HSF by cytoplasmic acidification, since inhibiting
proton efflux from cells triggers this same DNA binding and inhibition
of heat shock gene expression.