Multigenome DNA sequence conservation identifies Hox cis-regulatory elements
Abstract
To learn how well ungapped sequence comparisons of multiple species can predict cis-regulatory elements in Caenorhabditis elegans, we made such predictions across the large, complex ceh-13/lin-39 locus and tested them transgenically. We also examined how prediction quality varied with different genomes and parameters in our comparisons. Specifically, we sequenced ∼0.5% of the C. brenneri and C. sp. 3 PS1010 genomes, and compared five Caenorhabditis genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, and C. sp. 3 PS1010) to find regulatory elements in 22.8 kb of noncoding sequence from the ceh-13/lin-39 Hox subcluster. We developed the MUSSA program to find ungapped DNA sequences with N-way transitive conservation, applied it to the ceh-13/lin-39 locus, and transgenically assayed 21 regions with both high and low degrees of conservation. This identified 10 functional regulatory elements whose activities matched known ceh-13/lin-39 expression, with 100% specificity and a 77% recovery rate. One element was so well conserved that a similar mouse Hox cluster sequence recapitulated the native nematode expression pattern when tested in worms. Our findings suggest that ungapped sequence comparisons can predict regulatory elements genome-wide.
Footnotes
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↵3 Corresponding authors.
↵3 E-mail woldb{at}caltech.edu; fax (626) 395-5750.
↵3 E-mail pws{at}caltech.edu; fax (626) 568-8012.
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[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GenBank (http://www.ncbi.nlm.nih.gov/Genbank/) under accession nos. FJ362353–FJ36238.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.085472.108.
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- Received August 26, 2008.
- Accepted September 17, 2008.
- Copyright © 2008, Cold Spring Harbor Laboratory Press