Genomic-Functional Analyses-Conserved Noncoding Regions

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The major aims of the Genomic Functional Analysis Section are to identify cis-and trans-acting functional elements in vertebrate genomes using comparative analyses. The approach utilizes multi-species, whole-genome sequence alignments to identify conserved noncoding regions, examine patterns of sequence mutation within those elements, and test for changes in expression levels that correspond to changes in the sequences acquired through speciation events. Functional elements under consideration include any elements that comprise collections of transcription factor binding sites such as enhancers, silencers, promoters, and microRNA regulatory regions, elements that are exceptionally conserved, such as ultra-conserved elements, or those that contain uncharacterized structural features such as origins of replication. Collaborative efforts of mine with Penn State University have resulted in evolutionary analyses of promoters that study selection on TATA motifs or CpG islands by using multispecies sequence alignments of human/dog/mouse/chicken. A second study also utilizes sequence comparison to find putative regulatory motifs that control the expression of microRNA from nongenic locations. A related collaborative effort, with NHGRI, involves building a database to house microarray data from the ENCODE consortium. These important data contain information on transcription factor binding sites identified through ChIP-chip assays. The data are used as positive controls for the aforementioned predictions of genomic regulatory regions and for the identification of regions that are targets for future experimental analyses.