Collections > Electronic Theses and Dissertations > Allele-Specific Chromosome Conformation and its Association with Allelic Expression Bias

It is frequently suggested in recent literature that long-range interactions, presumably between enhancer elements and promoters, are an important factor in mediating gene expression. Such chromatin loops are often described as regulatory models in which active or repressive loops are suggested to exist as predominate chromosome conformations that are tightly associated with expression states. These models are supported by numerous investigations of well-studied models such as the beta-globin locus and the Hox clusters. If correct, it follows from these models that differential chromosome conformation patterns, under various contexts, should be a widely observable property of loci that exhibit differential gene expression. To test predictions of this hypothesis, seven candidate genes exhibiting strong allele-specific expression bias were selected for analysis with allele-specific 4C-Seq assays. Conditions for chromosome conformation experiments were optimized for a trophoblast stem cell model that is ideal for interrogating allele-specific chromatin and expression regulation. Results from these experiments demonstrate that the profile of observable interactions may vary between copies. This is important because many genomics assays do not typically detect resolution to discriminate between alleles. The observations made here help to demonstrate that assumption of behavior and modification of loci with genome-wide assays may introduce errors related to inability to distinguish whether events are occurring on both alleles in similar proportions or even at all.