Fig. 6: Augmented promoter H3K4me3 and pro-inflammatory gene activation.
a, Hi-C matrices (top) (bin size, 5 kb) and ChIP-seq tracks at the IL6 locus (bottom) in mock and SARS-CoV-2 conditions. White lines mark TADs, with intra-TAD interactions weakened throughout. Red asterisks show reduced H3K27ac peaks. Black arrows show enhanced H3K4me3 on IL6 promoter. Colour scale indicates Hi-C contact frequencies. b, A scatterplot showing the correlation between the ABC-P2 scores and true transcriptional changes in PIF genes (RPB1 ChIP-seq). Fold changes denote SARS-CoV-2/Mock. Error bands indicate the 95% confidence interval of the regression estimate. Pearson’s correlation coefficient is shown. c, Diagram of an IL6-promoter-driven mCherry reporter. d, Representative images of mCherry (red) and SARS-CoV-2 spike (S) protein (green) in cells carrying IL6-promoter-mCherry reporter under Mock or SARS-CoV-2 infection (0.1 MOI, 24 hpi). DAPI (blue). e, A model summarizing current observations of chromatin restructuring by SARS-CoV-2 infection at the 3D genome and epigenome scale. They are categorized from top to bottom in terms of A/B compartments, TADs/loop extrusion and enhancer–promoter contacts (see Extended Data Fig. 1a,b for additional information). These chromatin changes correlate with and may explain transcriptional deregulation of immuno-pathological gene deregulation in COVID-19 patients.
