Identification of a Coordinate Regulator of Interleukins 4, 13, and 5 by Cross-Species Sequence Comparisons
G. G. Loots,
12
R. M. Locksley,
3
C.
M. Blankespoor,
1
Z. E. Wang,
3
W. Miller,
4
E. M. Rubin,
1*
K. A. Frazer
1*
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.
1 Genome Sciences Department, Lawrence Berkeley
National Laboratory, Berkeley, CA 94720, USA.
2 Department of Molecular and Cell Biology,
University of California, Berkeley, CA 94720, USA.
3 Departments of Medicine and
Microbiology/Immunology and Howard Hughes Medical Institute, University
of California, San Francisco, CA 94143, USA.
4 Department of Computer Science and Engineering,
Pennsylvania State University, University Park, PA 16802, USA.
*
To whom correspondence should be addressed. E-mail:
kafrazer{at}lbl.gov (K.A.F.) and emrubin{at}lbl.gov (E.M.R.)
