Organization of MAO A and MAO B Promoters and Regulation of Gene Expression

Abstract

Monoamine oxidase (MAO) A and B play important roles in the metabolism of catecholamines and xenobiotics in the central nervous system and peripheral tissues. The ubiquitous presence of low level of MAO in all cells suggests essential functional for house keeping. Higher level of expression of MAO A and B also were observed in tissue and cell specific manner. The core promoter of human MAO A and B promoters have been characterized. Sp1 binding motifs were present in both promoters which constituted the major binding sites for Sp1 and Sp1-like family transcription factor binding, and other interaction proteins like Egr-1 in MAO B promoter. The presence of repeat units within the 2 kb human MAO A promoter which is associated with promoter activity and enzymatic activity in human fibroblast culture provided a tool to study human population with abnormal behaviors related to serotonin and other neurotransmitters. Conflicting results were reported from these studies due to the lack of basic understanding of MAO A promoter and the factors such as glucocorticoid which influences MAO A activity. Hopefully the enthusiasm will lead to more reliable tools to identify the major factor which caused the large difference in MAO A activity among human population. The overlapping Sp1/Egr-1/Sp1 binding site within MAO B promoter has been identified as the responsible element for PMA response. MAO B expression is selectively induced by the activation of protein kinase C and MAPK signal pathway.