TRANSCRIPTIONAL CONTROL OF NUCLEAR GENES FOR THE MITOCHONDRIAL MUSCLE ADP/ATP TRANSLOCATOR AND THE ATP SYNTHASE BETA-SUBUNIT - MULTIPLE FACTORS INTERACT WITH THE OXBOX REBOX PROMOTER SEQUENCES

The OXBOX promoter regions of the genes for the muscle-specific adenine nucleotide translocator (ANT1) and the beta subunit of the ATPsynthase (ATPsynbeta) have been implicated in the increased transcription of these nuclear-encoded oxidative phosphorylation (OXPHOS) genes in heart and skeletal muscle. DNA binding, electrophoretic mobility shift (gel-shift) assays now reveal that the OXBOX region has two unique but overlapping elements, the 13-base pair (bp) OXBOX and an 8-bp REBOX. The OXBOX binding factors are found only in myogenic cell lines, whereas the REBOX factors are ubiquitous. Methylation interference experiments have defined the boundaries of the OXBOX and REBOX elements, confirmed that the OXBOX factors are muscle-specific, and shown that the OXBOX and REBOX factors do not bind concurrently. The binding of the REBOX factors was found to be sensitive to NADH and thyroxine, suggesting that it may modulate OXPHOS gene expression in response to environmental and hormonal changes. Hence, the OXBOX/REBOX complex provides one mechanism by which mammalian energy metabolism can be adapted to developmental and environmental demands.