title: Genome-wide computational and expression analyses reveal G-quadruplex DNA motifs as conserved cis-regulatory elements in human and related species.
abstract: Using a combination of in silico and experimental approaches, we present evidence that the G-quadruplex (G4) motif (an alternative higher-order DNA conformation) has regulatory potential. Genome-wide analyses of 99980 human, chimpanzee, mouse, and rat promoters showed enrichment of sequence with potential to adopt G4 (potential G4 or PG4) motifs near transcription start sites (TSS; P < 0.0001), supporting earlier findings. Interestingly, we found >700 orthologously related promoters in human, mouse, and rat conserve PG4 motif(s). The corresponding genes have enriched (z score > 4.0) tissue-specific expression in 75 of 79 human tissues and are significantly overrepresented in signaling and regulation of cell-cycle (P < 10(-05)). This is supported by results from whole genome expression experiments in human HeLa S3 cells following treatment with TMPyP4 [5,10,15,20-tetra(N-methyl-4-pyridyl) porphine chloride], which is known to bind the G4 motif inside cells. Our results implicate G4-motif mediated regulation as a more general mode of transcription control than currently appreciated.
authors.affiliation: Proteomics and Structural Biology Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi 110 007, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Verma
authors.forename: Kangkan
authors.initials: K
authors.lastname: Halder
authors.forename: Rashi
authors.initials: R
authors.lastname: Halder
authors.forename: Vinod Kumar
authors.initials: VK
authors.lastname: Yadav
authors.forename: Pooja
authors.initials: P
authors.lastname: Rawal
authors.forename: Ram Krishna
authors.initials: RK
authors.lastname: Thakur
authors.forename: Farhan
authors.initials: F
authors.lastname: Mohd
authors.forename: Abhay
authors.initials: A
authors.lastname: Sharma
authors.forename: Shantanu
authors.initials: S
authors.lastname: Chowdhury