Promoter analysis of the human centromeric and telomeric survival motor neuron genes (SMN(C) and SMN(T))

Proximal spinal muscular atrophy (SMA) is caused by mutations in the telomeric (SMN(T)), but not centromeric (SMN(C)), survival motor neuron gene. Here we have identified and analyzed the two SMN promoters. We show that a 750-bp 5'-flanking fragment from each is capable of driving expression from a reporter construct. Within this fragment, we define a ~200-bp element that results in high expression in a motor neuron cell line. Sequence comparison of a 3.4-kb upstream fragment from each gene shows minimal differences. Although these differences produce a 2-fold difference in reporter activity between the two promoters, this is not sufficiently high to explain why SMN(T), but not SMN(C), is the disease determining gene. Our data thus demonstrate, for the first time, almost complete equivalence between the SMN promoters and rule out the important possibility that differences in them might explain why mutations in only the telomeric SMN gene cause SMA.