PT - JOURNAL ARTICLE AU - Mariano Barbieri AU - Sheila Q. Xie AU - Elena Torlai Triglia AU - InĂªs de Santiago AU - Miguel R. Branco AU - David Rueda AU - Mario Nicodemi AU - Ana Pombo TI - Active and poised promoter states drive folding of the extended <em>HoxB</em> locus in mouse embryonic stem cells AID - 10.1101/111773 DP - 2017 Jan 01 TA - bioRxiv PG - 111773 4099 - http://biorxiv.org/content/early/2017/02/28/111773.short 4100 - http://biorxiv.org/content/early/2017/02/28/111773.full AB - Gene expression states influence the three-dimensional conformation of the genome through poorly understood mechanisms. Here, we investigate the conformation of the murine HoxB locus, a gene-dense genomic region containing closely spaced genes with distinct activation states in mouse embryonic stem (ES) cells. To predict possible folding scenarios, we performed computer simulations of polymer models informed with different chromatin occupancy features, which define promoter activation states or CTCF binding sites. Single cell imaging of the locus folding was performed to test model predictions. While CTCF occupancy alone fails to predict the in vivo folding at genomic length scale of 10 kb, we found that homotypic interactions between active and Polycomb-repressed promoters co-occurring in the same DNA fibre fully explain the HoxB folding patterns imaged in single cells. We identify state-dependent promoter interactions as major drivers of chromatin folding in gene-dense regions.