There are two fundamental challenges facing the post-genome sequencing era: understanding the association between genome variation and disease and ascertaining the role of noncoding DNA in the evolution of complex genomes. Both of them are linked to mutations in gene regulatory elements that underlie evolutionary changes and population-specific differences in gene expression. In order to identify and characterize gene regulatory mutations, it is necessary to decipher the encryption of the gene regulatory code in the human and other complex genomes. We are combining comparative genomics, microarray expression data, libraries of transcription factor binding specificities, and pattern searches to develop a computational approach capable of “translating” the primal noncoding DNA sequence into signatures of tissue-specific regulatory elements. By using the combination of these complementary approaches, we were able to develop a computational method capable of predicting tissue-specific enhancers in loci of co-expressed genes, devising sequence profiles specific to tissue-specific enhancers, and characterizing the gene regulatory landscape of the human genome. In particular, I'll talk about our efforts to define and test experimentally the genetic encryption of heart regulatory elements.

L.A. Pennacchio, G.G. Loots, M.A. Nobrega, and I. Ovcharenko, Predicting Tissue-Specific Enhancers in the Human Genome, Genome Research, 17, 201-211, 2007.

I. Ovcharenko, G. Loots, M. Nobrega, R. Hardison, W. Miller, and L. Stubbs, Evolution and Functional Classification of Vertebrate Gene Deserts, Genome Research, 15(1), 137-145, 2005

M. Nobrega, I. Ovcharenko, V. Afzal, E. Rubin, Scanning Human Gene Deserts for Long-Range Enhancers, Science, 302(5644), 413, 2003