Mapping Regulatory Pathways in Cancers

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DESCRIPTION (provided by applicant): We propose to apply the emerging technology of Chromatin Immunoprecipitation on microarrays (ChIP chip) to identify the direct targets of transcription factors (TFs) known to be involved in breast and colon cancers. During the R21 phase of the project, we plan to identify these targets using a newly developed set of oligonucleotide microarrays that contain 15 million 50mer probes that tile through the non-repetitive sequence of the human genome at 100 bp resolution. We will validate that our ChIP chip protocols work with this new tiling array set. We will also develop and refine two new protocols, microarray reuse and 4-color hybridizations, that will allow economical use of this tiling array set so that it will be a more practical tool for research labs. In the R33 phase of this project, we will use this tiling array set to identify the direct targets of 9 TFs known to be involved in breast and colon cancers. Once we have collected the direct targets of these TFs, we will develop custom arrays that have probes that tile through all of the binding sites in the direct targets. We will use these TF focused screening arrays to study binding patterns in Icelandic breast and colon cancer samples to determine whether TF binding patterns could be a useful means of classifying tumors.