RT Journal
A1 Kuntz, Steven G.
A1 Schwarz, Erich M.
A1 DeModena, John A.
A1 De Buysscher, Tristan
A1 Trout, Diane
A1 Shizuya, Hiroaki
A1 Sternberg, Paul W.
A1 Wold, Barbara J.
T1 Multigenome DNA sequence conservation identifies Hox cis-regulatory elements
JF Genome Research 
JO Genome Research 
YR 2008 
FD December 01 
VO 18 
IS 12 
SP 1955 
OP 1968 
DO 10.1101/gr.085472.108 
UL http://genome.cshlp.org/content/18/12/1955.abstract 
AB 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.