International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Kirov S 1, Zhang B 1, Locascio P 2, Schmoyer D 1, Crawford O 1, Snoddy J 1

1 GST at Univ. of Tennessee/ORNL, Oak Ridge, United States, 2 Oak Ridge National Lab, Oak Ridge, United States

To understand the how RNA levels are regulated in cells, we have created a high-throughput, automated pipeline which can search for putative cis-regulatory elements (CREs) in the genome or other control regions within the upstream regions 5’ or 3’ UTRs of RNAs. 

We will present the structure of the pipeline and some results, including an example from a set of genes that form the cornified envelope.

This pipeline can input mouse gene sets that might be co-regulated (e.g. very similar gene expression changes under multiple perturbations, participation in a common biological process, etc.). The pipeline automatically retrieves appropriate sequences from the input gene sets. This pipeline also retrieves the relevant orthologs in other sequenced chordates. We use the orthologs to define evolutionarily conserved regions that are more likely to contain the motifs of interest. We search within these regions for short motifs that are overrepresented in the different ortholog sets.  These overrepresented motifs might be functional sites of interest. Typical results often include multiple sequence motifs that are present in a subset of the input gene set (e.g. several putative CREs in promoters shared among half the input genes). The second part of the pipeline is a search for these sequence motifs in the appropriate locations for all the genes in the genome. Frequently, our results from this search include the original genes and a modest number of genes with similar properties.  This process is partly confirmed, as it will sometimes uncover functional motifs that have been seen experimentally.

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