4.5 Article

Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models

Journal

GENOME BIOLOGY
Volume 17, Issue -, Pages -

Publisher

BMC
DOI: 10.1186/s13059-016-0909-0

Keywords

Chromosome conformation; Polymer model; Fluorescence in situ hybridization; cis-regulation

Funding

  1. Engineering and Physical Sciences Research Council [EP/I034661/1]
  2. European Research Council [648050 THREEDCELLPHYSICS]
  3. Medical Research Council [MC_UU_12009]
  4. Joint Research Councils [MR/K01577X/1]
  5. EPSRC [EP/I034661/1] Funding Source: UKRI
  6. MRC [MR/N00969X/1, MC_UU_12009/1, MC_UU_12009/15] Funding Source: UKRI
  7. Engineering and Physical Sciences Research Council [EP/I034661/1] Funding Source: researchfish
  8. Medical Research Council [MC_UU_12009/1, MC_UU_12009/15, MR/N00969X/1] Funding Source: researchfish

Ask authors/readers for more resources

The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations.

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