Identification of a coordinate regulator of interleukins 4, 13, and 5 by cross-species sequence comparisons

GG Loots, RM Locksley, CM Blankespoor, ZE Wang… - Science, 2000 - science.org
GG Loots, RM Locksley, CM Blankespoor, ZE Wang, W Miller, EM Rubin, KA Frazer
Science, 2000science.org
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 …
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.
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