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

Authors

  • M. Barbieri
  • S.Q. Xie
  • E. Torlai Triglia
  • A.M. Chiariello
  • S. Bianco
  • I. de Santiago
  • M.R. Branco
  • D. Rueda
  • M. Nicodemi
  • A. Pombo

Journal

  • Nature Structural & Molecular Biology

Citation

  • Nat Struct Mol Biol 24 (6): 515-524

Abstract

  • Gene expression states influence the 3D 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 that define promoter activation states or binding sites for the transcription factor CTCF. 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 fiber 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.


DOI

doi:10.1038/nsmb.3402