Monoamine oxidase A (
MAO A), encoded by the X chromosome, catalyzes the oxidative deamination of monoamine
neurotransmitters, such as
serotonin, and plays a critically important role in brain development and functions. Abnormal
MAO A activity has been implicated in several neuropsychiatric disorders, such as depression,
autism, and
attention deficit hyperactivity disorder, which show sexual dimorphism. However, the molecular basis for these disease processes is unclear. Recently, we found that
MAO A was a putative target gene directly regulated by a
transcription factor encoded by the sex-determining region Y (SRY) gene located on the Y chromosome. We demonstrated that SRY activates both
MAO A-promoter and catalytic activities in a human male
neuroblastoma BE(2)C cell line. A functional SRY-binding site in the
MAO A core promoter was identified and validated by electrophoretic mobility shift and
chromatin immunoprecipitation (ChIP) analyses. Coimmunoprecipitation and ChIP assays showed that SRY and Sp1 form a transcriptional complex and synergistically activate
MAO A transcription. This is the first study demonstrating that the Y-encoded
transcription factor SRY is capable of regulating an X-located gene, suggesting a novel molecular mechanism for sexual dimorphism in neural development, brain functions, and initiation/progression of neural disorders associated with
MAO A dysfunction.