title: Zinc-finger transcription factors are associated with guanine quadruplex motifs in human, chimpanzee, mouse and rat promoters genome-wide.
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.
authors: GNR Knowledge Centre for Genome Informatics, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India.
authors: Pankaj
authors: P
authors: Kumar
authors: Vinod Kumar
authors: VK
authors: Yadav
authors: Aradhita
authors: A
authors: Baral
authors: Parveen
authors: P
authors: Kumar
authors: Dhurjhoti
authors: D
authors: Saha
authors: Shantanu
authors: S
authors: Chowdhury
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D054856:G-Quadruplexes; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006147:Guanine / Q000032:analysis; D006801:Humans; D051379:Mice; D059372:Nucleotide Motifs; D002679:Pan troglodytes / Q000235:genetics; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D014157:Transcription Factors; D006147:Guanine