Regulation of MAO-A and MAO-B gene expression.
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 24 kb 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.
Shih
J C
JC
Department of Molecular Pharmacology and Toxicology, Pharmaceutical Science Center, University of Southern California, 1985 Zonal Ave. Los Angeles, California 90033, USA. jcshih@usc.edu
Chen
K
K
D000818:Animals; D001483:Base Sequence; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D008995:Monoamine Oxidase