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BIOLOGICAL SCIENCES / GENETICS
Identifying pattern-defined regulatory islands in mammalian genomes
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309
Communicated by Marvin H. Caruthers, University of Colorado, Boulder, CO, May 1, 2007 (received for review March 15, 2007)
Identifying cis-regulatory regions in mammalian genomes is a key challenge toward understanding transcriptional regulation. However, identification and functional characterization of those regulatory elements governing differential gene expression has been hampered by the limited understanding of their organization and locations in genomes. We hypothesized that genes that are conserved across species will also display conservation at the level of their transcriptional regulation and that this will be reflected in the organization of cis-elements mediating this regulation. Using a computational approach, clusters of transcription factor binding sites that are absolutely conserved in order and in spacing across human, rat, and mouse genomes were identified. We term these regions pattern-defined regulatory islands (PRIs). We discovered that these sequences are frequently active sites of transcriptional regulation. These PRIs occur in 
1.1% of the half-billion base pairs covered in the search and are located mainly in noncoding regions of the genome. We show that the premise of PRIs can be used to identify previously known and novel cis-regulatory regions controlling genes regulated by myogenic differentiation. Thus, PRIs may represent a fundamental property of the architecture of cis-regulatory elements in mammalian genomes, and this feature can be exploited to pinpoint critical transcriptional regulatory elements governing cell type-specific gene expression.
cis-regulatory elements | combinatorial regulation | computational prediction | myogenesis | transcription
*Present address: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305.
Present address: Dharmacon Research, Lafayette, CO 80026.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0704028104/DC1.
To whom correspondence should be addressed. E-mail: xuedong.liu{at}colorado.edu
© 2007 by The National Academy of Sciences of the USA
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