cneViewer: a database of conserved non-coding elements for studies of tissue-specific gene regulation

Persampieri, Jason; Ritter, Deborah; Lees, Daniel; Lehoczky, Jessica A.; Li, Qiang; Guo, Su; Chuang, Jeffrey H.

doi:10.1093/bioinformatics/btn443

Cited by 16 publications

(15 citation statements)

References 7 publications

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“…The zebrafishCNE database is well-suited for use with cneViewer (cneviewer.zebrafishcne.org) (Persampieri et al, 2008), a companion website to prioritize candidate zebrafish CNE sequences for experimental testing based on their proximity to genes of a desired tissue- and stage-specific expression, as well as other characteristics such as sequence identity, length, and synteny. Together the cneViewer website and the zebrafishCNE database create a workflow for the experimental researcher by simplifying experimental design, data storage, and analysis for zebrafish CNEs.…”

Section: Resultsmentioning

confidence: 99%

“…CNEs were then selected from amongst those with a minimum 60% identity and 100 bp conservation between zebrafish (zv6) and human (hg18), which are straightforward constraints relevant to our experimental organism and human. Most CNEs were chosen using cneViewer (cneviewer.zebrafishcne.org)(Persampieri et al, 2008), a tool that we have created to make use of publicly available zebrafish tissue and temporal gene expression data. cneViewer allows users to specify an anatomy and developmental timing and retrieve CNEs near genes expressed with that specificity.…”

Section: Methodsmentioning

confidence: 99%

“…As another verification, we applied the MobyDick maximum-likelihood motif detection algorithm (Bussemaker et al, 2000) to the 538 CNEs (>60% human-zebrafish identity, >100 bp) within 500kb of a curated set of 34 forebrain specific genes. Two of the motifs (gagcgg~gagggg: MobyDick gagggg p=1×10 −3 and tttcag: MobyDick ggtttcag p=1×10 −12 ) were found significant by Moby Dick, using the set of all remaining CNEs in the genome (Persampieri et al, 2008) for contrast. When the full experimental CNE set was completed, we counted the number of copies of the 5 motif strings in all experimental CNEs (on both the forward and reverse strands).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A systematic approach to identify functional motifs within vertebrate developmental enhancers

Ritter

Yang

et al. 2010

Developmental Biology

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Uncovering the cis-regulatory logic of developmental enhancers is critical to understanding the role of non-coding DNA in development. However, it is cumbersome to identify functional motifs within enhancers, and thus few vertebrate enhancers have their core functional motifs revealed. Here we report a combined experimental and computational approach for discovering regulatory motifs in developmental enhancers. Making use of the zebrafish gene expression database, we computationally identified conserved non-coding elements (CNEs) likely to have a desired tissue-specificity based on the expression of nearby genes. Through a high throughput and robust enhancer assay, we tested the activity of ~100 such CNEs and efficiently uncovered developmental enhancers with desired spatial and temporal expression patterns in the zebrafish brain. Application of de novo motif prediction algorithms on a group of forebrain enhancers identified five top-ranked motifs, all of which were experimentally validated as critical for forebrain enhancer activity. These results demonstrate a systematic approach to discover important regulatory motifs in vertebrate developmental enhancers. Moreover, this dataset provides a useful resource for further dissection of vertebrate brain development and function.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A systematic approach to identify functional motifs within vertebrate developmental enhancers

Ritter

Yang

et al. 2010

Developmental Biology

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“…There are several other resources on CNEs with partially overlapping objectives, in particular: CONDOR, CORG (23), cneViewer (24), Ancora, VISTA Enhancer browser, ECR browser and TFCONES (25). Despite a common theme, the scopes of these resources are quite different which makes a direct comparison difficult.…”

Section: Discussionmentioning

confidence: 99%

UCNEbase—a database of ultraconserved non-coding elements and genomic regulatory blocks

Dimitrieva¹,

Bücher²

2012

Nucleic Acids Research

115

120

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UCNEbase (http://ccg.vital-it.ch/UCNEbase) is a free, web-accessible information resource on the evolution and genomic organization of ultra-conserved non-coding elements (UCNEs). It currently covers 4351 such elements in 18 different species. The majority of UCNEs are supposed to be transcriptional regulators of key developmental genes. As most of them occur as clusters near potential target genes, the database is organized along two hierarchical levels: individual UCNEs and ultra-conserved genomic regulatory blocks (UGRBs). UCNEbase introduces a coherent nomenclature for UCNEs reflecting their respective associations with likely target genes. Orthologous and paralogous UCNEs share components of their names and are systematically cross-linked. Detailed synteny maps between the human and other genomes are provided for all UGRBs. UCNEbase is managed by a relational database system and can be accessed by a variety of web-based query pages. As it relies on the UCSC genome browser as visualization platform, a large part of its data content is also available as browser viewable custom track files. UCNEbase is potentially useful to any computational, experimental or evolutionary biologist interested in conserved non-coding DNA elements in vertebrates.

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“…However, there is little information about the functional roles of these conserved noncoding sequences (CNS), which, surprisingly, are often much more highly conserved than nucleotide sequences encoding well-conserved proteins. Comparisons of genomic sequences among various vertebrate species have revealed many CNS, which are known by various names (Ahituv et al 2005;Bejerano et al 2004;Dermitzakis et al 2002;Margulies et al 2003;Persampieri et al 2008;Prabhakar et al 2006;Sandelin et al 2004;Shin et al 2005;Siepel et al 2005; Thomas et al 2003;Venkatesh et al 2006;Visel et al 2008;Woolfe et al 2005). For instance, 2262 CNS (conserved nongenic; length C100 bp and identity C70%) were found by comparing human chromosome 21 and the syntenic mouse region (Dermitzakis et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of new long conserved noncoding sequences in vertebrates

et al. 2008

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Comparative sequence analyses have identified highly conserved genomic DNA sequences, including noncoding sequences, between humans and other species. By performing whole-genome comparisons of human and mouse, we have identified 611 conserved noncoding sequences longer than 500 bp, with more than 95% identity between the species. These long conserved noncoding sequences (LCNS) include 473 new sequences that do not overlap with previously reported ultraconserved elements (UCE), which are defined as aligned sequences longer than 200 bp with 100% identity in human, mouse, and rat. The LCNS were distributed throughout the genome except for the Y chromosome and often occurred in clusters within regions with a low density of coding genes. Many of the LCNS were also highly conserved in other mammals, chickens, frogs, and fish; however, we were unable to find orthologous sequences in the genomes of invertebrate species. In order to examine whether these conserved sequences are functionally important or merely mutational cold spots, we directly measured the frequencies of ENUinduced germline mutations in the LCNS of the mouse. By screening about 40.7 Mb, we found 35 mutations, including mutations at nucleotides that were conserved between human and fish. The mutation frequencies were equivalent to those found in other genomic regions, including coding sequences and introns, suggesting that the LCNS are not mutational cold spots at all. Taken together, these results Electronic supplementary materialThe online version of this article

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cneViewer: a database of conserved non-coding elements for studies of tissue-specific gene regulation

Cited by 16 publications

References 7 publications

A systematic approach to identify functional motifs within vertebrate developmental enhancers

A systematic approach to identify functional motifs within vertebrate developmental enhancers

UCNEbase—a database of ultraconserved non-coding elements and genomic regulatory blocks

Identification and characterization of new long conserved noncoding sequences in vertebrates

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