The core promoter region of human monoamine oxidase (MAO) A has been identified in the two 90 bp repeat sequences, which can be further divided into four imperfect tandem repeats, each containing an Sp 1 binding site in the reversed orientation. Gel retardation and DNase 1 footprinting assays identified Sp 1 to be the major transcription factor binding to MAO A core promoter. In addition, positive association has been observed between cellular Sp1 concentration and MAO A promoter or catalytic activity, indicating that Sp1 is a controlling factor for human MAO A expression. DNA fragments from MAO A core promoter exhibit promoter activity in both orientations in a transient transfection assay, using human growth hormone as the reporter gene. A DNA probe isolated from upstream of the core promoter detected positive signals in a Northern analysis, suggesting that the reverse promoter activity may endogenously transcribe a new gene located upstream of MAO A.