A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro.
A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro.
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DOI：
10.1093/nar/gkr882
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发表时间：
2012-02
影响因子：
14.9
通讯作者：
Balasubramanian S
中科院分区：
文献类型：
--
作者：
Raiber EA;Kranaster R;Lam E;Nikan M;Balasubramanian S
SP1是一种普遍存在的转录因子，参与各种管家基因的调控。已知其通过结合双链共有基序起作用。在这里，我们发现SP1也以高亲和力结合到非典型的DNA结构，G-四链体。特别是，我们已经研究了SP1的c-KIT癌基因的启动子区域内的结合位点，发现该网站可以折叠成一个反平行的两个四联体G-四链体。从细胞提取物的SP1下拉实验，连同生物物理结合试验表明，SP1具有可比的结合亲和力，这个G-四链体结构和典型的SP1双链体序列。使用SP1 ChIP芯片数据集，我们还发现87%的SP1结合位点与G-四链体形成序列重叠。此外，虽然这些免疫沉淀序列中的许多（36%）甚至缺乏最小的SP1共有基序，5′-GGGCGG-3′，我们已经表明，其中77%是推定的G-四链体。总的来说，这些数据表明，SP1是能够结合，典型的SP1双链体DNA以及G-四链体结构在体外，我们假设这两种类型的相互作用可能发生在细胞中。
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.
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