The human Aldolase C gene:transcriptional regulation and expression in the mammalian central nervous system

In mammals there are three different isoforms of the glycolytic enzyme aldolase, which are encoded by three different genes, namely, aldolase A (AldoA), aldolase B (AldoB) and aldolase C (AldoC). AldoC is the brain-specific form of aldolase and is selectively expressed in adult mammalian brain, mainly in the cerebellum. The promoter region of the AldoC gene, like other neuron-specific genes, lacks canonical TATA and CAAT boxes and contains multiple transcriptional start sites with a major one located -1340 bp from the methionine initiation codon in exon II. Two functionally different regions have been identified in the promoter of the human AldoC gene, a proximal and a distal region that are required for the complete transcription of the gene in in vitro and in vivo systems. The proximal region, located just upstream from the major transcriptional start site, is 164 bp long and drives the low-level brain-specific expression of the AldoC gene. The distal promoter region, spanning from -164 to -1200 bp with respect to the major transcriptional start site, contains a functional binding-site for transcriptional activators. This region mediates high-level AldoC transcription in the brain, AldoC transcriptional regulation by cAMP, and finally contributes to AldoC gene expression in the CA3 hippocampal neurons. The AldoC protein, and mRNA in some cases, are distributed in a stripe-like pattern in such areas of the human brain as the inferior cerebellar olives, the sensory neurons of the posterior horn of the spinal cord and the Purkinje cell layer of the cerebellum. This peculiar expression supports the hypothesis that the AldoC protein exerts other functions besides those characteristic of a glycolytic enzyme.