Significance
Dendritic cells (DCs), essential for immune responses, originate from bone marrow hematopoietic stem cells via intermediate progenitors. In eukaryotic nuclei, DNA is packaged into 3D chromatin structures that have been implicated in gene regulation. However, the chromatin structure reorganization dynamics during DC differentiation remain unknown. Here, we analyzed 3D chromatin structures in DCs and their progenitors. In genomic regions at DC-specific genes, the 3D chromatin structures were reorganized upon DC differentiation. The transcription factor IRF8 promoted chromatin structure changes in DC progenitors, leading to DC-specific gene induction. Strikingly, the chromatin structures of infection-inducible genes were preestablished in unstimulated DCs. Our findings advance the understanding of DC biology and basic principles of gene regulation for cell differentiation and host defense.