Integrated Epigenomics Analyses to Understand MicroRNA Transcriptional Regulation

The understanding of epigenetic mechanisms behind fundamental cellular processes, such as transcription, DNA repair and replication, and human diseases is necessary for a through understanding of human biology and the development of better treatment strategies. Nucleosome composition and positioning lies at the core of epigenetic regulation. Cellular signaling events directly or indirectly act to modify nucleosome composition and localization to induce responses to internal and external stimuli. The current nucleosome location mapping methods are low-throughput and labor-intensive, therefore not suitable for the in-depth genome-wide characterization of human chromatin structure. This dissertation describes the development of a global approach that can map nucleosome positions in the human genome in a high-throughput manner. Nucleosome positioning information obtained with this method was then utilized along with other epigenetics features such as chromatin modifications and RNA polymerase occupancy in an integrated fashion to identify microRNA promoter elements at high resolution. This work thus provided novel insight into the human chromatin structure and function, and showed how epigenetic features could be utilized to identify the functional regions of the human genome.