Regulation of MAO-A and MAO-B Gene Expression

• Published in: Current medicinal chemistry Vol. 11; no. 15; pp. 1995 - 2005
• Main Authors: Shih, J C, Chen, K
• Format: Journal Article
• Language: English
• Published: United Arab Emirates Bentham Science Publishers Ltd 01.08.2004
• Subjects: Animals; Base Sequence; Gene Expression Regulation, Enzymologic; Humans; Methylation; Molecular Sequence Data; Monoamine Oxidase - genetics; Monoamine Oxidase - metabolism; Sequence Homology, Nucleic Acid
• ISSN: 0929-8673; 1875-533X
• DOI: 10.2174/0929867043364757

MAO A and B genes are made of 15 exons with identical exon-intron organization. They are located on X-chromosome organized in opposite direction, tail to tail with 24kb apart. Both promoters are GC-rich and regulated by transcription factor Sp1. However, they have distinctly different features. MAO B gene, but not MAO A gene, has TATA box. MAO B promoter contains two clusters of overlapping Sp1 sites, the CACCC repressor element. Transcription factors Sp1 and Sp4 can activate MAO B promoter activity through the proximal cluster of Sp1 sites and its activation can be repressed by the over-expression of Sp3 and a related family member, BTEB2. Decreased methylation and transcription repressor Sp3 upregulate human MAO B, but not MAO A, gene expression during Caco-2 differentiation. MAO B, but not MAO A gene, could be activated by PMA (phorbol 12-myristate 13-acetate) by protein kinase C, MAPkinase signal transduction pathway involves cJun and Egr-1. The differences in MAO A and B gene regulation may explain the different tissue-specific expression and functions of these two important isoenzymes.