TY  - JOUR
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
Y1  - 2008/12/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1955 
EP  - 1968 
DO  - 10.1101/gr.085472.108 
VL  - 18 
IS  - 12 
UR  - http://genome.cshlp.org/content/18/12/1955.abstract 
N2  - 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. 
ER  -