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

Kumar, Pankaj ; Yadav, Vinod Kumar ; Baral, Aradhita ; Kumar, Parveen ; Saha, Dhurjhoti ; Chowdhury, Shantanu (2011) Zinc-finger transcription factors are associated with guanine quadruplex motifs in human, chimpanzee, mouse and rat promoters genome-wide Nucleic Acids Research, 39 (18). pp. 8005-8016. ISSN 0305-1048

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Official URL: http://nar.oxfordjournals.org/content/39/18/8005.a...

Related URL: http://dx.doi.org/10.1093/nar/gkr536

Abstract

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.

Item Type:Article
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