Conventional DCs (cDCs, comprised of the cDC1 and cDC2 subsets) efficiently present and cross-present antigens and produce cytokines such as IL-12 to prime T cell responses. Plasmacytoid DCs (pDCs) rapidly produce interferon-α/β and other soluble mediators in response to pathogen-derived nucleic acids. The differentiation and transcriptional signatures of each DC subset are determined by distinct combinations of transcription factors; however, how these factors enable rapid and specialized functional responses by DC subsets remained poorly understood. Our recent studies explored the role of higher-order chromatin organization in DC function. We combined chromatin profiling with genetic analysis to study the role of the cohesin complex, which organizes chromatin into topologically associated domains (TAD) to optimize transciption factor activity and enhancer-promoter interactions. We found that cohesin is critical for in vivo function of cDC1, including their ability to produce IL-12 and cross-prime anti-tumor responses. We also found that cohesin is required for the rapid production of IFN-α following pDC activation. In both cDC1 and pDC, cohesin was generally dispensable for activation, yet it selectively controlled key inducible genes such as Il12b and the Ifna locus. It also collaborated with the pioneer transcription factor IRF8 to preemptively reorganize the chromatin architecture, thereby enabling the anticipatory control of DC activation. Our ongoing studies explore the transcriptional and epigenetic control of DC maturation, an elaborate process that results in the migration of activated DC into lymph nodes and antigen presentation to T cells. DC maturation is controlled by several transcription factors including ETV3, which was recently described by our lab as a specific regulator of homeostatic DC maturation. Ongoing studies of these factors and of cohesin-mediated chromatin remodeling in the regulation of DC maturation will be discussed.