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J. Biol. Chem., Vol. 282, Issue 22, 15941-15945, June 1, 2007

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Minireview

Remote Control of Gene Expression^*

From the Cardiovascular Research Institute, University of Rochester School of Medicine, Rochester, New York 14642

The elucidation of a growing number of species' genomes heralds an unprecedented opportunity to ascertain functional attributes of non-coding sequences. In particular, cis regulatory modules (CRMs) controlling gene expression constitute a rich treasure trove of data to be defined and experimentally validated. Such information will provide insight into cell lineage determination and differentiation and the genetic basis of heritable diseases as well as the development of novel tools for restricting the inactivation of genes to specific cell types or conditions. Historically, the study of CRMs and their individual transcription factor binding sites has been limited to proximal regions around gene loci. Two important by-products of the genomics revolution, artificial chromosome vectors and comparative genomics, have fueled efforts to define an increasing number of CRMs acting remotely to control gene expression. Such regulation from a distance has challenged our perspectives of gene expression control and perhaps the very definition of a gene. This review summarizes current approaches to characterize remote control of gene expression in transgenic mice and inherent limitations for accurately interpreting the essential nature of CRM activity.

^* This minireview will be reprinted in the 2007 Minireview Compendium, which will be available in January, 2008. BAC work in the authors' laboratory is supported through National Institutes of Health Grants HL-62572 and HL-70077 and American Heart Association Grants 0625938T (to X. L.) and 0340075N (to J. M. M.).

The on-line version of this article (available at http://www.jbc.org) contains a supplemental table.

¹ To whom correspondence should be addressed. E-mail: j.m.miano{at}rochester.edu.

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