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Diffusion-Driven Looping Provides a Consistent Framework for Chromatin Organization

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  • Manfred Bohn
  • Dieter W Heermann

Abstract

Chromatin folding inside the interphase nucleus of eukaryotic cells is done on multiple scales of length and time. Despite recent progress in understanding the folding motifs of chromatin, the higher-order structure still remains elusive. Various experimental studies reveal a tight connection between genome folding and function. Chromosomes fold into a confined subspace of the nucleus and form distinct territories. Chromatin looping seems to play a dominant role both in transcriptional regulation as well as in chromatin organization and has been assumed to be mediated by long-range interactions in many polymer models. However, it remains a crucial question which mechanisms are necessary to make two chromatin regions become co-located, i.e. have them in spatial proximity. We demonstrate that the formation of loops can be accomplished solely on the basis of diffusional motion. The probabilistic nature of temporary contacts mimics the effects of proteins, e.g. transcription factors, in the solvent. We establish testable quantitative predictions by deriving scale-independent measures for comparison to experimental data. In this Dynamic Loop (DL) model, the co-localization probability of distant elements is strongly increased compared to linear non-looping chains. The model correctly describes folding into a confined space as well as the experimentally observed cell-to-cell variation. Most importantly, at biological densities, model chromosomes occupy distinct territories showing less inter-chromosomal contacts than linear chains. Thus, dynamic diffusion-based looping, i.e. gene co-localization, provides a consistent framework for chromatin organization in eukaryotic interphase nuclei.

Suggested Citation

  • Manfred Bohn & Dieter W Heermann, 2010. "Diffusion-Driven Looping Provides a Consistent Framework for Chromatin Organization," PLOS ONE, Public Library of Science, vol. 5(8), pages 1-14, August.
  • Handle: RePEc:plo:pone00:0012218
    DOI: 10.1371/journal.pone.0012218
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    Cited by:

    1. Lara Connolley & Lucas Schnabel & Martin Thanbichler & Seán M. Murray, 2023. "Partition complex structure can arise from sliding and bridging of ParB dimers," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Manfred Bohn & Dieter W Heermann, 2011. "Repulsive Forces Between Looping Chromosomes Induce Entropy-Driven Segregation," PLOS ONE, Public Library of Science, vol. 6(1), pages 1-8, January.
    3. Mattia Conte & Ehsan Irani & Andrea M. Chiariello & Alex Abraham & Simona Bianco & Andrea Esposito & Mario Nicodemi, 2022. "Loop-extrusion and polymer phase-separation can co-exist at the single-molecule level to shape chromatin folding," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    4. Ofir Shukron & David Holcman, 2017. "Transient chromatin properties revealed by polymer models and stochastic simulations constructed from Chromosomal Capture data," PLOS Computational Biology, Public Library of Science, vol. 13(4), pages 1-20, April.

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