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Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells

By Mariano Barbieri, Sheila Q Xie, Elena Torlai Triglia, InĂªs de Santiago, Miguel R Branco, David S. Rueda, Mario Nicodemi, Ana Pombo

Posted 28 Feb 2017
bioRxiv DOI: 10.1101/111773 (published DOI: 10.1038/nsmb.3402)

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.

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