Journal
CURRENT MEDICINAL CHEMISTRY
Volume 11, Issue 15, Pages 1995-2005Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867043364757
Keywords
MAO A; MAO B; gene regulation; promoter; Sp1; protein kinase C; MAPkinase; Egr-1
Funding
- NIMH NIH HHS [R37 MH39085, R01 MH37020] Funding Source: Medline
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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.
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