Chromatin structure undergoes global and local reorganization during classical dendritic cell differentiation and activation

Classical dendritic cells (cDCs) are essential for immune responses and differentiate from hematopoietic stem cells via intermediate progenitors, such as common DC progenitors (CDPs). Chromatin structures, including nuclear compartments and topologically associating domains (TADs) have been implicated in gene regulation. However, it remains unknown the extent and dynamics of their reorganization during cDC development and activation. Here, we performed a comprehensive analysis of chromatin structure in DC progenitors and cDC subpopulations. A shift from the inactive to the active compartment occurred at cDC gene loci in CDPs, which was followed by the reorganization of TADs. The transcription factor IRF8 mediated changes into the active compartment in DC progenitors, likely leading to DC-specific gene induction. Strikingly, the structure of host defense-related gene loci was pre-established in unstimulated cDCs, suggesting an important contribution for rapid immune responses against pathogens. Our data provide a fundamental understanding of genome reorganization in cDC differentiation and activation.