Genomic rearrangements are often causal to malignant transformation. Rearrangements can disrupt a tumor-suppressor gene or generate an oncogene by gene fusion. However, many rearrangements have been found in non-coding regions, excluding that they contribute to oncogenic transformation through the disruption or creation of proteins. Since gene expression can be influenced by the gene environment, it is likely that rearrangements in non-coding regions cause transcriptional aberrations and thereby contribute to malignant transformation. In this project I therefore aim to elucidate how gene environment and genomic interaction domains influence the regulation of gene expression by: - determining how the formation of interaction domains is influenced by genomic rearrangements, by performing Chromosome Conformation Capture analyses after creating rearrangements at a single model locus as well as genome-wide. - analyzing how induced transcriptional activity affects the activity of neighboring genes, and if this depends on the boundaries of interaction domains, by allele-specific expression analysis after induced transcriptional activity at the model locus as well as in a high-throughput genome-wide manner. Altogether this project will elucidate how gene environment influences transcriptional regulation. These findings will be instrumental to understand how translocations in non-coding regions can lead to malignant transformation.