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A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro

2011; Oxford University Press; Volume: 40; Issue: 4 Linguagem: Inglês

10.1093/nar/gkr882

1362-4962

Eun‐Ang Raiber, Ramon Kranaster, Enid Y.N. Lam, Mehran Nikan, Shankar Balasubramanian,

Genomics and Chromatin Dynamics

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 0 -GGGCGG-3 0 , 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.