Transcriptional regulation of the SPAST gene encoding spastin (SPG4). A
) Cartoon showing the human SPAST promoter structure with cis-elements representing putative transcription factor (TF) binding sites for NRF1, SOX11, and Sp1. As is typical of CpG-promoters, transcription start sites (TSS) are spread over a large region in exon 1, with two major TSS positions indicated by arrows . There are two alternative translational initiation codons for spastin 68 and 60 kDa polypeptide isoforms, respectively . B) Multi-sequence alignment of conserved TF cis-elements in representative mammalian species. Sequences were aligned using ClustalW 2.1 and manually adjusted as needed for maximum parsimony. Evolutionarily conserved TF motifs are indicated; *, nucleotide positions conserved in all 19 species; ∧, nucleotide positions conserved in 17/19 species; yellow shading, highly conserved SOX11 motif; red, NRF1 motifs; purple, Sp1 motifs. The NRF1 and SOX11 motifs are highly conserved, but only one Sp1 motif near the 5′ TSS is conserved in mammals. Extended alignments of the complete promoter region into exon 1 and including the first translational start codon are shown in Fig. S1.