Cell fate decisions entail organized changes in gene expression. A fundamental question in biology is how genes and regulatory regions are organized and coordinated for transcription regulation in these processes. Recent findings, including those of the Bischof team, have demonstrated that alterations in chromatin architecture play a decisive role in gene-regulation, but their importance in cell-fate decisions is still unclear. To close this important gap in our knowledge, we seek to explore the role of chromatin structure changes in cellular senescence, a cell-fate crucial for tumor suppression and aging. We hypothesize that active co-regulated genes and their regulatory factors coalesce in enhancer-promoter hot spots optimized for efficient and coordinated transcriptional control to enforce the senescence phenotype. To prove this hypothesis correct, we will combine genome-wide gene expression, epigenome and chromatin structure studies in cells undergoing senescence and leverage the expertise of the Bischof lab in these domains and my own expertise in high-throughput sequencing and transcriptomic data analyses.