A transcriptional enhancer from the coding region of ADAMTS5.
BACKGROUND
The revelation that the human genome encodes only approximately 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.


RESULTS
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
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.
Barthel
Kristen K B
KK
Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado, United States of America.
Liu
Xuedong
X
D051722:ADAM Proteins / Q000235:genetics*; D000071116:ADAMTS5 Protein; D000818:Animals; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004742:Enhancer Elements, Genetic; D005091:Exons; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D009132:Muscles / Q000378:metabolism; D016296:Mutagenesis; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D014157:Transcription Factors; D051722:ADAM Proteins; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human