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A Transcriptional Enhancer from the Coding Region of ADAMTS5

Kristen K. B. Barthel,Xuedong Liu

Published 2008 in PLoS ONE

ABSTRACT

Background The revelation that the human genome encodes only ∼25,000 genes and thus cannot account for phenotypic complexity has been one of the biggest surprises in the post-genomic era. However, accumulating evidence suggests that transcriptional regulation may be in large part responsible for this observed mammalian complexity. Consequently, there has been a strong drive to locate cis-regulatory regions in mammalian genomes in order to understand the unifying principles governing these regions, including their genomic distribution. Although a number of systematic approaches have been developed, these all discount coding sequence. Methodology/Principal Findings Using the computational tool PRI (Pattern-defined Regulatory Islands), which does not mask coding sequence, we identified a regulatory region associated with the gene ADAMTS5 that encompasses the entirety of the essential coding exon 2. We demonstrate through a combination of chromatin immunoprecipitation and reporter gene studies that this region can not only bind the myogenic transcription factors MYOD and myogenin and the E-protein HEB but can also function as a very strong myogenic transcriptional enhancer. Conclusions/Significance Thus, we report the identification and detailed characterization of an exonic enhancer. Ultimately, this leads to the interesting question of why evolution would be so parsimonious in the functional assignment of sequence.

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