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. 2009 Feb 25:10:92.
doi: 10.1186/1471-2164-10-92.

Genome-scale identification of Caenorhabditis elegans regulatory elements by tiling-array mapping of DNase I hypersensitive sites

Affiliations

Genome-scale identification of Caenorhabditis elegans regulatory elements by tiling-array mapping of DNase I hypersensitive sites

Baochen Shi et al. BMC Genomics. .

Abstract

Background: A major goal of post-genomics research is the integrated analysis of genes, regulatory elements and the chromatin architecture on a genome-wide scale. Mapping DNase I hypersensitive sites within the nuclear chromatin is a powerful and well-established method of identifying regulatory element candidates.

Results: Here, we report the first genome-wide analysis of DNase I hypersensitive sites (DHSs) in Caenorhabditis elegans. The data was obtained by hybridizing DNase I-treated and end-captured material from young adult worms to a high-resolution tiling microarray. The data show that C. elegans DHSs were significantly enriched within intergenic regions located 2 kb upstream and downstream of coding genes, and also that a considerable fraction of all DHSs mapped to intergenic positions distant to annotated coding genes. Annotated transcribed loci were generally depleted in DHSs relative to intergenic regions, but DHSs were nonetheless enriched in coding exons and UTRs, whereas introns were significantly depleted in DHSs. Many DHSs appeared to be associated with annotated non-coding RNAs and recently detected transcripts of unknown function. It has been reported that nematode highly conserved non-coding elements were associated with cis-regulatory elements, and we also found that DHSs, particularly distal intergenic DHSs, were significantly enriched in regions that were conserved between the C. elegans and C. briggsae genomes.

Conclusion: We describe the first genome-wide analysis of C. elegans DHSs, and show that the distribution of DHSs is strongly associated with functional elements in the genome.

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Figures

Figure 1
Figure 1
Protocol outline for the genome-scale mapping of C. elegans DHSs by tiling microarray analysis.
Figure 2
Figure 2
Gel electrophoresis of DNase I – digested nuclear DNA.
Figure 3
Figure 3
Chromosomal DHS densities.
Figure 4
Figure 4
DHS genomic locations. "Proximal" and "nearby" have the same meaning, and refer to locations within 2 kb from the transcriptional start sites (TSSs) or transcription termination site (TTSs) of the nearest coding genes. "Distal" intergenic locations correspondingly refer to locations more than 2 kb from a TSS or TTS. "Multiples" refers to DHSs located within loci annotated with more than one coding transcript, and "span" means DHSs spanning junctions between exons and introns.
Figure 5
Figure 5
Distribution of intergenic DHSs relative to transcriptional start sites (TSSs) or transcription termination sites (TTSs) of the nearest coding genes.
Figure 6
Figure 6
DHS distribution relative to gene expressional characteristics. Relationship between the distributions of DHSs and genes expressed at young adult stage. The Pearson correlation coefficients were calculated between the frequency of DHSs and YA genes in 1 Mb non-overlapping windows along each chromosome.
Figure 7
Figure 7
An example of a DHS located within the known promoter region of a coding gene expressed at the adult stage.
Figure 8
Figure 8
An example of a DHS located in an exon between two intronic snoRNAs.

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