Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons.
Long-range regulatory elements are difficult to discover experimentally; however, they tend to be conserved among mammals, suggesting that cross-species sequence comparisons should identify them. To search for regulatory sequences, we examined about 1 megabase of orthologous human and mouse sequences for conserved noncoding elements with greater than or equal to 70% identity over at least 100 base pairs. Ninety noncoding sequences meeting these criteria were discovered, and the analysis of 15 of these elements found that about 70% were conserved across mammals. Characterization of the largest element in yeast artificial chromosome transgenic mice revealed it to be a coordinate regulator of three genes, interleukin-4, interleukin-13, and interleukin-5, spread over 120 kilobases.
Loots
G G
GG
Genome Sciences Department, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Locksley
R M
RM
Blankespoor
C M
CM
Wang
Z E
ZE
Miller
W
W
Rubin
E M
EM
Frazer
K A
KA
D000818:Animals; D001483:Base Sequence; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics*; D016547:Kinesins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D020161:Physical Chromosome Mapping; D012045:Regulatory Sequences, Nucleic Acid; D029701:Saccharomyces cerevisiae Proteins; D013045:Species Specificity; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019076:Transgenes
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D018793:Interleukin-13; D015848:Interleukin-5; C087415:KIF3A protein, human; C490202:Kif3a protein, mouse; C086930:RAD50 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015847:Interleukin-4; D016547:Kinesins