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Science 7 April 2000:
Vol. 288. no. 5463, pp. 136 - 140
DOI: 10.1126/science.288.5463.136
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Reports

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.)

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H. L. Keen, M. J. Ryan, A. Beyer, S. Mathur, T. E. Scheetz, B. D. Gackle, F. M. Faraci, T. L. Casavant, and C. D. Sigmund (2004)
Physiol Genomics 18, 33-42
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Long-range activation of Sox9 in Odd Sex (Ods) mice.
Y. Qin, L.-k. Kong, C. Poirier, C. Truong, P. A. Overbeek, and C. E. Bishop (2004)
Hum. Mol. Genet. 13, 1213-1218
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eShadow: A Tool for Comparing Closely Related Sequences.
I. Ovcharenko, D. Boffelli, and G. G. Loots (2004)
Genome Res. 14, 1191-1198
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CD28 Costimulation Controls Histone Hyperacetylation of the Interleukin 5 Gene Locus in Developing Th2 Cells.
M. Inami, M. Yamashita, Y. Tenda, A. Hasegawa, M. Kimura, K. Hashimoto, N. Seki, M. Taniguchi, and T. Nakayama (2004)
J. Biol. Chem. 279, 23123-23133
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Ultraconserved Elements in the Human Genome.
G. Bejerano, M. Pheasant, I. Makunin, S. Stephen, W. J. Kent, J. S. Mattick, and D. Haussler (2004)
Science 304, 1321-1325
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IL-4-Induced GATA-3 Expression Is a Time-Restricted Instruction Switch for Th2 Cell Differentiation.
N. Seki, M. Miyazaki, W. Suzuki, K. Hayashi, K. Arima, E. Myburgh, K. Izuhara, F. Brombacher, and M. Kubo (2004)
J. Immunol. 172, 6158-6166
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Comparison of Human Chromosome 21 Conserved Nongenic Sequences (CNGs) With the Mouse and Dog Genomes Shows That Their Selective Constraint Is Independent of Their Genic Environment.
E. T. Dermitzakis, E. Kirkness, S. Schwarz, E. Birney, A. Reymond, and S. E. Antonarakis (2004)
Genome Res. 14, 852-859
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