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Caenorhabditis elegans cisRED: a catalogue of conserved genomic elements.

Sleumer MC, Bilenky M, He A, Robertson G, Thiessen N, Jones SJ - Nucleic Acids Res. (2009)

Bottom Line: We annotated 26% of the motifs as similar to known binding sequences of transcription factors from ORegAnno, TRANSFAC and JASPAR.This is the first catalogue of annotated conserved upstream elements for nematodes and can be used to find putative regulatory elements, improve gene models, discover novel RNA genes, and understand the evolution of transcription factors and their binding sites in phylum Nematoda.The annotated motifs provide novel binding site candidates for both characterized transcription factors and orthologues of characterized mammalian transcription factors.

View Article: PubMed Central - PubMed

Affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.

ABSTRACT
The availability of completely sequenced genomes from eight species of nematodes has provided an opportunity to identify novel cis-regulatory elements in the promoter regions of Caenorhabditis elegans transcripts using comparative genomics. We determined orthologues for C. elegans transcripts in C. briggsae, C. remanei, C. brenneri, C. japonica, Pristionchus pacificus, Brugia malayi and Trichinella spiralis using the WABA alignment algorithm. We pooled the upstream region of each transcript in C. elegans with the upstream regions of its orthologues and identified conserved DNA sequence elements by de novo motif discovery. In total, we discovered 158 017 novel conserved motifs upstream of 3847 C. elegans transcripts for which three or more orthologues were available, and identified 82% of 44 experimentally proven regulatory elements from ORegAnno. We annotated 26% of the motifs as similar to known binding sequences of transcription factors from ORegAnno, TRANSFAC and JASPAR. This is the first catalogue of annotated conserved upstream elements for nematodes and can be used to find putative regulatory elements, improve gene models, discover novel RNA genes, and understand the evolution of transcription factors and their binding sites in phylum Nematoda. The annotated motifs provide novel binding site candidates for both characterized transcription factors and orthologues of characterized mammalian transcription factors.

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Examples of experimentally proven sites. (A) A motif that overlaps a PHA-4 site upstream of tph-1 (ZK1290.2b). (B) A motif that overlaps a DAF-12 site upstream of lit-1 (W06F12.1c). (C) A motif that overlaps an ‘Early-2’ site upstream of K07C11.4. Locations of experimentally proven sites are indicated by black boxes. cisRED URLs are indicated in Table 1.
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Figure 4: Examples of experimentally proven sites. (A) A motif that overlaps a PHA-4 site upstream of tph-1 (ZK1290.2b). (B) A motif that overlaps a DAF-12 site upstream of lit-1 (W06F12.1c). (C) A motif that overlaps an ‘Early-2’ site upstream of K07C11.4. Locations of experimentally proven sites are indicated by black boxes. cisRED URLs are indicated in Table 1.

Mentions: Discovered motifs were compared to experimentally proven TFBSs from the literature to gauge the success of the motif discovery process. For the 44 experimentally proven sites in the upstream regions under examination, 36 (82%) overlapped with motifs by at least 50% of the TFBS width, and 29 (66%) overlapped a motif completely. A complete list of experimentally proven sites and all cisRED motifs that overlapped them is shown in Supplementary Table S5. For example, the following sites were found: the PHA-4 site near tph-1 (ZK1290.2b) (29) (Figure 4A), a DAF-12 site near lit-1 (W06F12.1c) (30) (Figure 4B) and an ‘Early-2’ motif near K07C11.4 described by Gaudet et al. (4) (Figure 4C). Of the eight known sites that were not found, seven were poorly conserved and one was a low-complexity PHA-4 site.Figure 4.


Caenorhabditis elegans cisRED: a catalogue of conserved genomic elements.

Sleumer MC, Bilenky M, He A, Robertson G, Thiessen N, Jones SJ - Nucleic Acids Res. (2009)

Examples of experimentally proven sites. (A) A motif that overlaps a PHA-4 site upstream of tph-1 (ZK1290.2b). (B) A motif that overlaps a DAF-12 site upstream of lit-1 (W06F12.1c). (C) A motif that overlaps an ‘Early-2’ site upstream of K07C11.4. Locations of experimentally proven sites are indicated by black boxes. cisRED URLs are indicated in Table 1.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651782&req=5

Figure 4: Examples of experimentally proven sites. (A) A motif that overlaps a PHA-4 site upstream of tph-1 (ZK1290.2b). (B) A motif that overlaps a DAF-12 site upstream of lit-1 (W06F12.1c). (C) A motif that overlaps an ‘Early-2’ site upstream of K07C11.4. Locations of experimentally proven sites are indicated by black boxes. cisRED URLs are indicated in Table 1.
Mentions: Discovered motifs were compared to experimentally proven TFBSs from the literature to gauge the success of the motif discovery process. For the 44 experimentally proven sites in the upstream regions under examination, 36 (82%) overlapped with motifs by at least 50% of the TFBS width, and 29 (66%) overlapped a motif completely. A complete list of experimentally proven sites and all cisRED motifs that overlapped them is shown in Supplementary Table S5. For example, the following sites were found: the PHA-4 site near tph-1 (ZK1290.2b) (29) (Figure 4A), a DAF-12 site near lit-1 (W06F12.1c) (30) (Figure 4B) and an ‘Early-2’ motif near K07C11.4 described by Gaudet et al. (4) (Figure 4C). Of the eight known sites that were not found, seven were poorly conserved and one was a low-complexity PHA-4 site.Figure 4.

Bottom Line: We annotated 26% of the motifs as similar to known binding sequences of transcription factors from ORegAnno, TRANSFAC and JASPAR.This is the first catalogue of annotated conserved upstream elements for nematodes and can be used to find putative regulatory elements, improve gene models, discover novel RNA genes, and understand the evolution of transcription factors and their binding sites in phylum Nematoda.The annotated motifs provide novel binding site candidates for both characterized transcription factors and orthologues of characterized mammalian transcription factors.

View Article: PubMed Central - PubMed

Affiliation: Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.

ABSTRACT
The availability of completely sequenced genomes from eight species of nematodes has provided an opportunity to identify novel cis-regulatory elements in the promoter regions of Caenorhabditis elegans transcripts using comparative genomics. We determined orthologues for C. elegans transcripts in C. briggsae, C. remanei, C. brenneri, C. japonica, Pristionchus pacificus, Brugia malayi and Trichinella spiralis using the WABA alignment algorithm. We pooled the upstream region of each transcript in C. elegans with the upstream regions of its orthologues and identified conserved DNA sequence elements by de novo motif discovery. In total, we discovered 158 017 novel conserved motifs upstream of 3847 C. elegans transcripts for which three or more orthologues were available, and identified 82% of 44 experimentally proven regulatory elements from ORegAnno. We annotated 26% of the motifs as similar to known binding sequences of transcription factors from ORegAnno, TRANSFAC and JASPAR. This is the first catalogue of annotated conserved upstream elements for nematodes and can be used to find putative regulatory elements, improve gene models, discover novel RNA genes, and understand the evolution of transcription factors and their binding sites in phylum Nematoda. The annotated motifs provide novel binding site candidates for both characterized transcription factors and orthologues of characterized mammalian transcription factors.

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