| For decades, gene regulation has been understood as essential in human biology. Until recently, gene regulation has been studied only on a small scale, but today, genome-wide identification of regulatory elements is an important challenge facing biologists. Through significant advances in technology and concerted efforts of the genomics community, we have made significant progress in achieving the goal of understanding regulation in the human genome. This document details a series of genomic studies aimed at identifying and characterizing regulatory elements in the genome. Our work developing the tools to characterize a class of bidirectional promoters laid the foundation for a more comprehensive study of promoters in the ENCODE (Encyclopedia of DNA Elements) regions. The combination of these studies resulted in the largest collection of functionally validated human promoters available. In additional studies we characterized binding sites of two essential transcription factors, the Heat Shock Transcription Factor 1 (HSF1) and the Serum Response Factor (SRF). In two separate studies we identified dozens of novel targets for these transcription factors, characterizing the role each plays in response to environmental stimuli. SRF has been particularly interesting due to its essential role in muscle and brain development. Exploring these factors provided more than just a catalog of binding sites---the binding sites of these and other transcription factor provide insight into important biological pathways and mechanisms. Expanding similar studies to each of the nearly 2000 transcription factors in the human genome presents a great and exciting challenge that will provide a great resource for understanding human disease and physiology. |
