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

Abstract

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.

GeneHancer: genome-wide integration of enhancers and target genes in GeneCards

“…The score is computed based on a combination of evidence annotations using the following components: (i) the proportion of supporting enhancer sources ($S_{\mathrm{normals}\mathrm{normalo}\mathrm{normalu}\mathrm{normalr}\mathrm{normalc}\mathrm{normale}\mathrm{normals}}$ —count of sources divided by 4, the maximum number of sources); (ii) overlap with conserved regions from UCNE (44) ($S_{\mathrm{normalc}\mathrm{normalo}\mathrm{normaln}\mathrm{normals}\mathrm{normale}\mathrm{normalr}\mathrm{normalv}\mathrm{normale}\mathrm{normald}}$, 1 for enhancers overlapping with a conserved region, 0 otherwise); and (iii) TFBSs score: for each enhancer, the count of unique TFs having a TFBS within the enhancer was calculated and normalized as follows: $S_{\mathrm{normalT}\mathrm{normalF}\mathrm{normalB}\mathrm{normalS}}=\frac{{\mathrm{normall}\mathrm{normalo}\mathrm{normalg}}_{10}(1+\mathrm{normalc}\mathrm{normalo}\mathrm{normalu}\mathrm{normaln}\mathrm{normalt})}{{\mathrm{normall}\mathrm{normalo}\mathrm{normalg}}_{10}(1+\mathrm{normalmax}\left(\mathrm{normalc}\mathrm{normalo}\mathrm{normalu}\mathrm{normaln}\mathrm{normalt}\right))}$. The TFBSs used for this calculation were mined from ENCODE ChIP-Seq datasets, as described in the ‘Transcription factor co-expression analysis’ paragraph in the Supplementary Methods.…”

Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments

“…S3C, right). A set of complex loci of significantly greater length than average (Mann-Whitney U-test P < 10 À15 ) overlap ultraconserved noncoding elements, regulatory blocks or archipelagos (Akalin et al 2009;Montavon and Duboule 2012;Dimitrieva and Bucher 2013). These loci were preferentially down-regulated in cohesin-deficient thymocytes (Supplemental Fig.…”

A quantitative-PCR based method to estimate ranavirus viral load following normalisation by reference to an ultraconserved vertebrate target

“…The nucleotide sequence of our target region (EBF3N) was also shown to be highly similar across amphibian, reptile, and some fish species. The primer and/or probe sequences would, however, require modification prior to use with some fish species due to the lower degree of UCNE sequence conservation in this class as observed in the current study and highlighted by others (Dimitrieva and Bucher, 2013). This complements work by Holopainen et al (2011) by extending the range of the normalising host qPCR from a few fish species, to most vertebrates.…”

“…UCNEbase is an online database containing human UCNE sequences and their orthologs in eight other species (Dimitrieva and Bucher, 2013). Human UCNEs with greater than 90% sequence identity to Xenopus tropicalis (the only amphibian species in the database) were downloaded from UCNEbase.…”

“…Ultraconserved non-coding elements (UCNEs) are non-coding regions, more than 200 base pairs (bp) in length that share ultra-high sequence identity among vertebrates (Dimitrieva and Bucher, 2013). These are promising candidate targets for a broadly applicable normalising hostqPCR because: 1) they are highly conserved, allowing the design of minimally degenerate primers and probe; 2) they are encoded in the nuclear genome (as opposed to mitochondrial) meaning that, assuming the sequence is present at a single copy in the haploid genome, target copy number equates to an approximate cell quantity; 3) they are of sufficient length to enable qPCR primer and probe design; and 4) they are only present in vertebrates (Bejerano et al, 2004;Retelska et al, 2007) minimising the risk of non-specific amplification due to non-host DNA present in a sample, such as from bacteria, fungi, or parasites.…”