Research accomplishments 1. We have identified an interaction between obesity and the landscape of regulatory DNA in the mouse colon. Our experiments define a pattern of enhancer utilization in the colon that resembles cancer progression and is initiated by obesity. 2. We have investigated tissue specificity to chromatin modification and gene regulation in mice. We discovered that CpG islands utilize many common regulatory features regardless of tissue type. However, each tissue fine-tunes this pattern in a specific manner. 3. We studies the impact of a specific mutation in GATA3 on properties of the protein. GATA3 is a DNA-binding transcription factor that is mutated at high frequency in breast cancer. Using a cell line (MCF7) with a tumor specific mutation, we determined that mutation leads to dramatic increase in stability of GATA3 and associated transcription factors in the face of hormonal challenge. 4. We have made significant progress in understanding the genomic distribution of NuRD complex in breast cancer cells and how this enzyme contributes to the biological program of breast cancer. 6. We have begun analysis of genome modification in an exposure model of cancer.
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