| In this thesis I present a thorough functional genomics analysis of nuclear receptor binding sites in the breast cancer cell line MCF7. In Chapter 1 I give an overview of nuclear receptors, review several important nuclear receptors and their functions in cancer, and review recent progress in nuclear receptor mediated transcriptional regulation. In Chapter 2 I present the genome-wide binding site mapping and analysis of twenty four nuclear receptors (NRs) and fourteen NR co-factors in MCF7. I demonstrate the importance of hotspots in transcriptional regulation, and propose that Peroxisome Proliferator-Activated Receptor Delta (PPARdelta) plays an important role in breast cancer. In Chapter 3 I present further analyses of nuclear receptor binding sits in MCF7 cells using a new technique I co-developed called "enhancer-seq", which gives quantitative measurements of enhancer activities on a genome scale. Enhancer-seq will have broad applications in the field of genomics. |
