The Juicer analysis tool was used to perform read alignment and read pairing and deduplication for each Hi-C replicates (48). Reads with a low mapping quality score (<30) were removed. Reads across replicates for each condition were merged. Juicebox was used for Hi-C contact map visualization, which was plotted with 5 kb resolution. TAD sizes were calculated using the Arrowhead function from Juicer tools. All Hi-C analysis was performed on data that are publicly available through the Gene Expression Omnibus database (BJ cells: GSE81087; A549 cells: GSE92819 for control cells and GSE92811 for DXM treatment). Reads from raw Hi-C data from BJ cells were mapped to the hg19 genome, and Hi-C data from A549 cells were mapped to the hg38 human reference genome with Mbo I as the restriction enzyme. Contact probability as a function of genomic distance was calculated by normalizing observed contacts to expected contacts (i.e., possible pairs at a given genomic distance apart). A linear regression fit on the log-log relationship between genomic distance and contact probability was performed. The mean and SE for contact probability scaling was calculated from the slope of the regression and the SE for this parameter estimate, respectively. To determine whether the difference of contact probability scaling between two treatment conditions was significant, we assumed that contact probability scaling for each condition follows a normal distribution with SD equal to the root mean square error of the regression residuals. P values were calculated by performing a paired Student’s t test assuming unequal variance.

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