Chromatin architecture plays a crucial role in gene expression and cellular responses across various biological processes, including differentiation, immune response to pathogens, and cancer progression. While gene regulation is often studied on an expression level independently of chromatin structure, our work highlights the importance of including nucleosome dynamics over proteincoding gene promoters to better understand a more complete picture of genome response in both differentiation and disease. We found that nucleosome distribution is altered over a specific subset of promoters during monocyte differentiation and immune responses to bacterial and viral stimuli. These changes in distribution were associated with genes specific to each stimulus. In contrast, HP1 knockout during cancer progression resulted in minimal nucleosome redistribution, with no clear enrichment in biological pathways. This suggests that nucleosome remodeling in differentiation and immune responses is highly targeted, whereas nucleosome redistribution in cancer may be more stochastic. In addition to nucleosome redistribution, we observed widespread changes in nucleosome susceptibility to nuclease digestion across all conditions studied. In contrast to the fewer than 10% of nucleosomes which were repositioned, more than 60% of promoters exhibited altered nuclease accessibility in monocyte differentiation, immune stimulation, and cancer progression. Time-course analyses revealed rapid, stimulus-specific chromatin responses to differentiation cues and immune challenges. In lung cells, exposure to coronavirus nucleocapsid proteins induced distinct changes in nucleosome accessibility, with genes affected by these alterations playing key roles in disease pathology. Finally, our investigation into promoter dynamics in cancer progression identified HP1β as a central regulator of susceptibility to nuclease, suggesting that its disruption may contribute to chromatin remodeling observed in other conditions. Data from this study are under consideration for publication. Findings from the second and third chapters were recently submitted to the Journal of Leukocyte Biology and posted to bioRxiv under the following doi numbers: 10.1101/2025.02.11.637695 and 10.1101/2025.02.11.637703. Data from the fourth chapter is being prepared for submission to the Journal of Virology and will be posted to bioRxiv in the near future.