rVISTA 2.0: evolutionary analysis of transcription factor binding sites

Abstract

Identifying and characterizing the transcription factor binding site (TFBS) patterns of cis-regulatory elements represents a challenge, but holds promise to reveal the regulatory language the genome uses to dictate transcriptional dynamics. Several studies have demonstrated that regulatory modules are under positive selection and, therefore, are often conserved between related species. Using this evolutionary principle, we have created a comparative tool, rVISTA, for analyzing the regulatory potential of noncoding sequences. Our ability to experimentally identify functional noncoding sequences is extremely limited, therefore, rVISTA attempts to fill this great gap in genomic analysis by offering a powerful approach for eliminating TFBSs least likely to be biologically relevant. The rVISTA tool combines TFBS predictions, sequence comparisons and cluster analysis to identify noncoding DNA regions that are evolutionarily conserved and present in a specific configuration within genomic sequences. Here, we present the newly developed version 2.0 of the rVISTA tool, which can process alignments generated by both the zPicture and blastz alignment programs or use pre-computed pairwise alignments of several vertebrate genomes available from the ECR Browser and GALA database. The rVISTA web server is closely interconnected with the TRANSFAC database, allowing users to either search for matrices present in the TRANSFAC library collection or search for user-defined consensus sequences. The rVISTA tool is publicly available at http://rvista.dcode.org/.

Expression of TLE3 by bone marrow stromal cells is regulated by canonical Wnt signaling

“…For identification of transcription factor binding sites, DNA sequences were first aligned using zPicture [29] then transferred to rVista 2.0 [30]. Amino-acid homology between human and mouse TLE3 were determined by using Protein-protein BLAST (blastp) analysis.…”

“…rVista2.0 [30] analysis of this 2.5 kbp region allowed us to identify binding sites for transcription factors that may regulate adipogenesis and/or osteoblastogenesis, such as TCF/LEF and C/EBPs [43][44][45]. We next generated the TLE3 (3.0) luciferase reporter construct containing this 2.5 kbp ECR conserved fragment of the 5 0 flanking region of murine tle3 gene and examined the effect of Wnt3a, C/EBPa, or C/EBPb, predicted to regulate promoter of TLE3 by rVista2.0 analysis, on this reporter activity.…”

Marine Organism Cell Biology and Regulatory Sequence Discoveryin Comparative Functional Genomics

“…Second, gene expression often results from coordinate activation of multiple, proximal regulatory elements; therefore identifying TFBSs in clusters, rather than isolation, may enhance confidence in the functionality of predicted TFBSs. These principles have been leveraged, albeit differently, by rVISTA (http:// gsd.lbl.gov/vista/index.shtml; Loots et al 2002;Loots and Ovcharenko 2004), which is a member of the VISTA suite of tools and is also integrated with zPicture, and the newly launched Mulan (http://mulan.dcode.org/; Ovcharenko et al 2005). Both servers use profiles of transcription factor binding sites from the TRANSFAC database (http://www.biobase.de; Matys et al 2003).…”

Hypomethylation of proximal CpG motif of interleukin-10 promoter regulates its expression in human rheumatoid arthritis

“…Alignments between mouse and human IL10 loci, and between macaque and human IL10 loci were performed, and the extent of DNA sequence homology was computed with a web-based program called Regulatory Visualization Tools for Alignment (rVISTA; http://www.gsd.lbl.gov/vista) [18] . The plot of the percentage of sequence identity referred to the human sequence.…”