Capture Hi-C and MNase Seq data of a 2.3 Mb region of human chromosome 12 (chr12: 6,140,000-8,460,000) containing GAPDH and NANOG loci in human IMR90 fibroblasts (hFibs) and fibroblast-derived human induced pluripotent stem cell (hiPSCs). MiOS, an integrated imaging and modeling strategy to resolve gene folding at basepair resolution

The linear sequence of DNA provides invaluable information about the nature of genes, the regulatory elements and their distribution along chromosomes. However, to fully understand gene function and regulation we need to dissect how genes are physically folded in the 3-D nuclear space. Here we describe immuno-OligoSTORM (iOS), an imaging strategy to simultaneously image the DNA and histones in super-resolution to resolve the distribution of nucleosomes within specific genes at the nanoscale level. We combined iOS with an innovative coarse-grained modeling approach to integrate the super resolution imaging data with Hi-C contact frequencies and deconvoluted MNase-seq information. This novel method, called Modeling immuno-OligoSTORM (MiOS), allows quantitative modeling of genes at basepair resolution. With MiOS we explored intercellular variability and transcriptional dependent gene conformation of housekeeping and pluripotency-related genes in human pluripotent and differentiated cells with the highest degree of data integration achieved so far.