SP1 is a ubiquitous transcription factor that is involved in the regulation of 
various house-keeping genes. It is known that it acts by binding to a 
double-stranded consensus motif. Here, we have discovered that SP1 binds also to 
a non-canonical DNA structure, a G-quadruplex, with high affinity. In 
particular, we have studied the SP1 binding site within the promoter region of 
the c-KIT oncogene and found that this site can fold into an anti-parallel 
two-tetrad G-quadruplex. SP1 pull-down experiments from cellular extracts, 
together with biophysical binding assays revealed that SP1 has a comparable 
binding affinity for this G-quadruplex structure and the canonical SP1 duplex 
sequence. Using SP1 ChIP-on-chip data sets, we have also found that 87% of SP1 
binding sites overlap with G-quadruplex forming sequences. Furthermore, while 
many of these immuoprecipitated sequences (36%) even lack the minimal SP1 
consensus motif, 5'-GGGCGG-3', we have shown that 77% of them are putative 
G-quadruplexes. Collectively, these data suggest that SP1 is able to bind both, 
canonical SP1 duplex DNA as well as G-quadruplex structures in vitro and we 
hypothesize that both types of interactions may occur in cells.