J Biol Chem, Vol. 274, Issue 12, 8077-8084, March 19, 1999

Genes for the Human Mitochondrial Trifunctional Protein - and -Subunits Are Divergently Transcribed from a Common Promoter Region

Kenji E. Orii^§, Koji O. Orii, Masayoshi Souri^§, Tadao Orii, Naomi Kondo, Takashi Hashimoto^§, and Toshifumi Aoyama^§**

From the  Department of Pediatrics, Gifu University School of Medicine, Gifu 500-8076, Japan, ^§ Department of Biochemistry and ^** Department of Aging Biochemistry, Research Center on Aging and Adaptation, Shinshu University School of Medicine, Matsumoto 390-8621, Japan, and  Department of Human Welfare, Faculty of Human Welfare, Chubu Gakuin University, Seki 501-3936, Japan

Human HADHA and HADHB genes encode the subunits of an enzyme complex, the trifunctional protein, involved in mitochondrial -oxidation of fatty acids. Both genes are located in the same region of chromosome 2p23. We isolated genomic clones, including 5' flanking regions, for HADHA and HADHB. Sequencing revealed that both of these genes are linked in a head-to-head arrangement on opposite strands and have in common a 350-bp 5' flanking region. The 5' flanking region has bidirectional promoter activity within this region; two cis elements proved critical for the activity. Transcription factor Sp1 functions as an activator for the bidirectional promoter by binding to both elements. Therefore, expression of trifunctional protein subunits are probably coordinately regulated by a common promoter and by Sp1.