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

Shi B, Guo X, Wu T, Sheng S, Wang J, Skogerbø G, Zhu X, Chen R - BMC Genomics (2009)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Laboratory and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China. shibaochen@moon.ibp.ac.cn

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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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.
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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.

Mentions: A statistical simulation (Monte Carlo simulation) was performed to determine the distribution bias of DHSs relative to annotated genomic elements. It has been estimated that approximately 60% of the total C. elegans genome is transcribed as protein-coding genes based on the annotation of WormBase WS140 [8]. In this study, we found that C. elegans DHSs were significantly depleted in intragenic regions (p-value < 0.001, see Supplemental Table S1 in Additional file 1). A supplemental table listing the confirmed coding genes with nearby DHSs was provided in Additional file 2. Approximately 40% of the C. elegans DHSs map unequivocally within the bounds of protein coding loci (Figure 4). Around 2.17% of all DHSs were located to the first coding exons, which represent an enrichment compared to the random set (p-value < = 0.053). In contrast to human DHSs, which are significantly depleted in internal (i.e. non-first) exons [4], there appear to be no statistical differences in DHS locations with respect to exon positions in the nematode. The 10.2% DHSs found in intronic locations represent, on the other hand, a significant depletion compared to the random set (p-value < 0.001), suggesting that intragenic regulatory elements in C. elegans are predominantly located in coding sequence. The few percent of the DHSs residing within 5' and 3' UTRs represented a slight enrichment over a random distribution (p-value < = 0.057). In addition to the 40% of the DHSs with a certain genic location, 12.8% of DHSs mapped to loci annotated with several different and/or overlapping transcripts, and the precise genomic status of these DHSs could not be determined.


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

Shi B, Guo X, Wu T, Sheng S, Wang J, Skogerbø G, Zhu X, Chen R - BMC Genomics (2009)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651899&req=5

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.
Mentions: A statistical simulation (Monte Carlo simulation) was performed to determine the distribution bias of DHSs relative to annotated genomic elements. It has been estimated that approximately 60% of the total C. elegans genome is transcribed as protein-coding genes based on the annotation of WormBase WS140 [8]. In this study, we found that C. elegans DHSs were significantly depleted in intragenic regions (p-value < 0.001, see Supplemental Table S1 in Additional file 1). A supplemental table listing the confirmed coding genes with nearby DHSs was provided in Additional file 2. Approximately 40% of the C. elegans DHSs map unequivocally within the bounds of protein coding loci (Figure 4). Around 2.17% of all DHSs were located to the first coding exons, which represent an enrichment compared to the random set (p-value < = 0.053). In contrast to human DHSs, which are significantly depleted in internal (i.e. non-first) exons [4], there appear to be no statistical differences in DHS locations with respect to exon positions in the nematode. The 10.2% DHSs found in intronic locations represent, on the other hand, a significant depletion compared to the random set (p-value < 0.001), suggesting that intragenic regulatory elements in C. elegans are predominantly located in coding sequence. The few percent of the DHSs residing within 5' and 3' UTRs represented a slight enrichment over a random distribution (p-value < = 0.057). In addition to the 40% of the DHSs with a certain genic location, 12.8% of DHSs mapped to loci annotated with several different and/or overlapping transcripts, and the precise genomic status of these DHSs could not be determined.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Bioinformatics Laboratory and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China. shibaochen@moon.ibp.ac.cn

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.

Show MeSH