Journal article
Regulation of monoamine oxidase A by the SRY gene on the Y chromosome
The FASEB journal, Vol.23(11), pp.4029-4038
11/2009
PMCID: PMC2775015
PMID: 19661285
Abstract
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.—Wu, J. B., Chen, K., Li, Y., Lau, Y.-F. C., Shih, J. C. Regulation of monoamine oxidase A by the
SRY
gene on the Y chromosome.
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Details
- Title
- Regulation of monoamine oxidase A by the SRY gene on the Y chromosome
- Creators
- Jason B Wu - Washington State University, Pharmaceutical Sciences, Department ofKevin Chen - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, andYunmin Li - University of California, San FranciscoYun-Fai Chris Lau - Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, andJean C Shih - University of Southern California
- Publication Details
- The FASEB journal, Vol.23(11), pp.4029-4038
- Academic Unit
- Pharmacy and Pharmaceutical Sciences, College of
- Publisher
- The Federation of American Societies for Experimental Biology
- Identifiers
- 99900620488801842
- Language
- English
- Resource Type
- Journal article