A novel G‐quadruplex motif modulates promoter activity of human <i>thymidine kinase 1</i>

Basundra, Richa; Kumar, Anuj; Amrane, Samir; Verma, Anjali; Phan, Anh Tuân; Chowdhury, Shantanu

doi:10.1111/j.1742-4658.2010.07814.x

Cited by 22 publications

(26 citation statements)

References 64 publications

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“…This sequence consists of consecutive GG-repeats with the potential to fold into a non-canonical G-quadruplex structure with two stacked guanine tetrads rather than the three tetrads that have commonly featured in most genomic G-quadruplexes. While some G-quadruplex motif search algorithms have been based on a minimum of three G-tetrads (34,37), biophysical experiments have supported G-quadruplex formation with just two tetrads, as it is the case for the thrombin binding DNA aptamer 5′-GGT TGG TGT GGT TGG-3′ (38) and more recently, a quadruplex motif within the promoter of human thymidine kinase 1 (39). …”

Section: Resultsmentioning

confidence: 99%

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

Raiber¹,

Kranaster²,

Lam³

et al. 2011

Nucleic Acids Research

183

164

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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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Section: Resultsmentioning

confidence: 99%

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

Raiber¹,

Kranaster²,

Lam³

et al. 2011

Nucleic Acids Research

183

164

View full text Add to dashboard Cite

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“…[5][6][7][8][9][10][11][12][13][14][15][16][17] Recently, there are also a few reports about the structures and biological functions of two-quartet G-quadruplexes, like the promoters of oncogene HIF1ɑ and TK1 57,58. Our findings suggest that more attentions should be paid to the structure and function of G 2 sequences.…”

mentioning

confidence: 83%

Two-Quartet G-Quadruplexes Formed by DNA Sequences Containing Four Contiguous GG Runs

et al. 2015

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The DNA sequence containing four contiguous GG runs (G2NxG2NyG2NzG2, G2 sequence) has the potential to form a two-quartet G-quadruplex. However, the prevalence, structure, and function of G2 sequences have not been well-studied. Here, bioinformatics analysis reveals the abundance of G2 sequences in the human genome and their enrichment in promoter regions. The density of G2 sequences in the genome and promoters is much higher than that of the G3 sequence (G3NxG3NyG3NzG3). Experiments show that the conformations and thermal stabilities of the two-quartet G-quadruplexes of G2 sequences are highly sensitive to the length and composition of the loops. Among the two-quartet G-quadruplexes, the parallel G-quadruplex with a loop length of 1 and the antiparallel G-quadruplex with a loop length of 3 show high thermal stabilities. Additionally, the stable parallel G-quadruplexes are stacked into intermolecular higher-order structures. This work determines the prevalence of G2 sequences in the human genome and demonstrates that the G-quadruplex structures for certain loop lengths and compositions may be stable in vivo. Thus, more attention should be paid to the structure and function of the two-quartet G-quadruplex.

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“…The program was rerun with cytosine (C) instead of guanine (G) to identify motifs on the complimentary strand and appropriately corrected for strand orientation. We restricted our program to a stem size of 3 and loop length of 1–7 considering that most in vitro characterizations and experiments have used these guidelines for PG4 motifs, though recent work shows that non-canonical motifs are also possible with varying loop and stem sizes (5,19,26). …”

Section: Methodsmentioning

confidence: 99%

“…Similarly, transcription was influenced by G-quadruplex-forming sequence motifs within the core promoter of human c- KIT (16) and k-RAS oncogenes (17). Promoter-G-quadruplex were also reported for a number of other genes such as VEGF , PDGF , HIF1α , BCL-2 , RB and RET (18) in addition to thymidine kinase 1 , where a non-canonical G-quadruplex motif formed from repeats constituting two guanines instead of three was found to be functionally active (19). In line with these studies, transcriptome profiling performed in human cancer cells indicated changes in gene expression in presence of established intracellular G-quadruplex binding ligands suggesting a genome-wide role of G-quadruplex motifs in transcription (20).…”

Section: Introductionmentioning

confidence: 95%

Zinc-finger transcription factors are associated with guanine quadruplex motifs in human, chimpanzee, mouse and rat promoters genome-wide

Kumar

Yadav

Baral

et al. 2011

Nucleic Acids Research

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Function of non-B DNA structures are poorly understood though several bioinformatics studies predict role of the G-quadruplex DNA structure in transcription. Earlier, using transcriptome profiling we found evidence of widespread G-quadruplex-mediated gene regulation. Herein, we asked whether potential G-quadruplex (PG4) motifs associate with transcription factors (TF). This was analyzed using 220 position weight matrices [designated as transcription factor binding sites (TFBS)], representing 187 unique TF, in >75 000 genes in human, chimpanzee, mouse and rat. Results show binding sites of nine TFs, including that of AP-2, SP1, MAZ and VDR, occurred significantly within 100 bases of the PG4 motif (P < 1.24E-10). PG4–TFBS combinations were conserved in ‘orthologously’ related promoters across all four organisms and were associated with >850 genes in each genome. Remarkably, seven of the nine TFs were zinc-finger binding proteins indicating a novel characteristic of PG4 motifs. To test these findings, transcriptome profiles from human cell lines treated with G-quadruplex-specific molecules were used; 66 genes were significantly differentially expressed across both cell-types, which also harbored conserved PG4 motifs along with one/more of the nine TFBS. In addition, genes regulated by PG4–TFBS combinations were found to be co-regulated in human tissues, further emphasizing the regulatory significance of the associations.

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A novel G‐quadruplex motif modulates promoter activity of human thymidine kinase 1

Cited by 22 publications

References 64 publications

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

Two-Quartet G-Quadruplexes Formed by DNA Sequences Containing Four Contiguous GG Runs

Zinc-finger transcription factors are associated with guanine quadruplex motifs in human, chimpanzee, mouse and rat promoters genome-wide

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