Abstract
The highly organized three-dimensional genome is crucial for gene transcription. However, it remains elusive how the order of the genome architecture related to its function. Here, we developed a single-cell Hi-C method and proposed TAD “degree of disorder” as a measure of genome organizational patterns, which is correlated with the chromatin epigenetic states, gene expression and co-regulation, and chromatin structure variability in individual cells. Upon Mycobacterium tuberculosis infection, NF-κB enters into the nucleus, binds to the target genome regions and initiates systematic chromatin conformation reorganization. Furthermore, we identified a remote NF-κB enriched enhancer promotes the expression of PD-L1 through chromatin loop, which could be a potential anti-tuberculosis and even anti-tumor therapeutic target. The integrated Hi-C, eQTL, and GWAS analysis depicted the atlas of the long-range target genes of tuberculosis susceptible loci. Among which SNP rs1873613 is located in the anchor of a dynamic chromatin loop with LRRK2, whose inhibitor AdoCbl could be an anti-tuberculosis drug candidate. Our study provides comprehensive resources for the 4D genome of immunocytes and sheds insights into the genome organization order and the coordinated gene transcription.