Promoter organization and activity of human monoamine oxidase (MAO) A and B genes.
Monoamine oxidase A and B (MAO A and B) play important roles in the metabolism of biogenic and dietary amines and are encoded by two genes derived from a common ancestral gene. The promoter regions for human MAO A and B genes have been characterized using a series of 5' flanking sequences linked to a human growth hormone reporter gene. When these constructs were transfected into NIH3T3, SHSY-5Y, and COS7 cells, the maximal promoter activity for MAO A was found in a 0.14 kilobase (kb) PvuII/DraII fragment (A0.14) and in a 0.15 kb PstI/NaeI fragment (B0.15) for MAO B. Both fragments are GC-rich, contain potential Sp1 binding sites, and are in the region where the MAO A and B 5' flanking sequences share the highest identity (approximately 60%). However, the organization of the transcription elements is distinctly different between these two promoters. Fragment A0.14 consists of three Sp1 elements, all in reversed orientations, and lacks a TATA box. Two of the Sp1 sites are located within the downstream 90 base pair (bp) direct repeat, and the third is located at the 3' end of the upstream 90 bp direct repeat. Fragment B0.15 contains an Sp1-CACCC-Sp1-TATA structure; deletion of any of these elements reduced promoter activity. Additional Sp1 sites, CACCC elements, CCAAT boxes, and direct repeats (four 30 bp direct repeats in MAO A and two 29 bp direct repeats in MAO B) are found in farther-upstream sequences of both genes (1.27 kb for MAO A and mostly in 0.2 kb for MAO B). Inclusion of these sequences decreased promoter activity. The different promoter organization of MAO A and B genes provides the basis for their different tissue- and cell-specific expression.
Zhu
Q S
QS
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033.
Grimsby
J
J
Chen
K
K
Shih
J C
JC
D016475:3T3 Cells / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005796:Genes; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D013237:Stereoisomerism; D016385:TATA Box
D004247:DNA; D008995:Monoamine Oxidase