UC San Diego

Gene expression in animals is finely controlled by cis-regulatory elements in the non-coding sequences, yet the mechanisms by which they regulate transcription are not fully understood. During my graduate study, I dissected the molecular mechanisms of CTCF-mediated transcriptional insulation, explored the mechanisms of how monomethylation on histone H3 lysine 4 (H3K4me1) facilitates enhancer function, and finally, characterized the dynamic regulatory landscape during mouse embryonic development. Chapter 1 is an overview of the (epi)genomics field. I introduce the background of my three research projects and summarize the major findings. In chapter 2, I systematically introduce my research on the mechanisms of CTCF-mediated transcriptional insulation. I investigate the context-specific insulator function of CTCF bound DNA elements using an insulator reporter assay in mouse embryonic stem cells. I demonstrate that insulation strength depends on the number of CTCF binding sites in tandem, the upstream flanking sequences, and the 9-11 zinc fingers of CTCF protein. Further, I find insulators are sufficient to create chromatin boundaries and reduce enhancer-promoter communications. In chapter 3, colleagues and I identify multiple proteins associated with H3K4me1 in the nucleus. We demonstrate that H3K4me1 facilitates the recruitment of BAF complex on active enhancers. The details of other projects of my graduate research are not included in this dissertation.