@article{Cis-regulatory:1791,
      recid = {1791},
      author = {Montefiori, Lindsey Elizabeth},
      title = {Genetic and Genomic Approaches to Investigate the Roles of  Cis-regulatory Elements in Development and Disease},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2019-06},
      pages = {161},
      abstract = {Gene regulation describes the totality of molecular events  that result in precisely orchestrated gene expression  patterns which collectively drive organismal development  and define cellular states. Much of this logic is encoded  in the genome itself, which is subject to mutation and  natural variation. Because of the fundamental role that  gene regulation plays in cellular biology, perturbations to  gene expression patterns may have pathophysiological  consequences, and these are far from being well understood.  In my dissertation research, I used a variety of  experimental and computational approaches to study the  genetic basis of gene regulation in the context of normal  cellular development and human disease. First, I developed  an experimental approach to improve the ATAC-seq assay, a  commonly used assay to detect regulatory elements. This  approach uses CRISPR/Cas9 to remove contaminating  mitochondrial DNA fragments, increasing the number of  regulatory elements identified. Next, I investigated the  gene-regulatory function of two ultraconserved enhancer  elements in the mouse genome. I used CRISPR/Cas9 genome  engineering to delete these elements from the germline and  reported that deletion of one element caused a body weight  phenotype, albeit in the absence of gene expression changes  in the hypothalamus, challenging our view of these elements  as traditional enhancers. Finally, I used promoter capture  Hi-C in combination with gene expression profiling and  publicly available epigenetic datasets to study the  gene-regulatory changes that accompany human cardiomyocyte  differentiation. I integrated these data with 50  genome-wide association study results for cardiovascular  disease traits in order to prioritize target genes for  functional follow up studies and provide a gene regulatory  context to the thousands of loci associated with these  diseases. Taken together, this work improved our ability to  assay functional regions of the genome with experimental  approaches, contributed further data to the function of  ultraconserved elements, and increased our understanding of  the complex nature of long-range gene regulation in the  context of cardiomyocyte differentiation and cardiovascular  disease.},
      url = {http://knowledge.uchicago.edu/record/1791},
      doi = {https://doi.org/10.6082/uchicago.1791},
}