infection induces chromatin restructuring in host cells to activate immune responses.

BACKGROUND

spp., facultative intracellular pathogens that cause brucellosis, drive pathogenesis by invading host cells and establishing intracellular persistence. While their molecular mechanisms are well-characterized, how induces chromatin restructuring in host cells remains poorly understood, representing a critical gap in host-pathogen interaction research.

METHODS

Using an established infection model of -infected RAW264.7 murine macrophages, we integrated Hi-C, ATAC-seq, and RNA-seq to generate multi-omics datasets. Multidimensional comparative genomics approaches were employed to systematically map infection-induced changes in host chromatin architecture and functional genomic organization.

RESULTS

Our findings unveiled substantial alterations in the host chromatin architecture, characterized by a reduction in B-B compartment regions interactions, an increase in A-B compartment interactions, and diminished long-range chromatin contacts. Crucially, reshaped chromatin compartmentalization, activating interferon-stimulated genes (ISGs) in regions transitioning from compartment B to A. Enhanced sub-TADs interactions within ISG clusters further facilitated their coordinated expression. Additionally, infection remodeled chromatin loop structures, strengthening interactions linked to immune-related gene activation.

CONCLUSION

These results demonstrate that host cells undergo substantial chromatin remodeling during acute infection as a defense mechanism against pathogen invasion. Our findings provide critical insights into host-pathogen interactions and suggest potential epigenetic targets for managing brucellosis.