DNA supercoiling plays important roles in gene expression regulation, although, the underlying mechanisms whereby DNA supercoiling modulates gene expression remain elusive. The fact that the transcription process itself generates DNA supercoiling has further complicated the issue. Transcription-driven DNA supercoiling is local and transient. Such a DNA supercoiling effect is likely to play important roles in controlling complex gene expression regulation. Using the suppression of the leu-500 mutation in Salmonella typhimurium topA mutants as a model system, we put forward our view of the effects of transcription-driven DNA supercoiling on gene expression control.