Format

Send to

Choose Destination
Nucleic Acids Res. 2016 May 5;44(8):3503-12. doi: 10.1093/nar/gkw135. Epub 2016 Apr 8.

Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.

Author information

1
SUPA, School of Physics & Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK.
2
Department of Plant Sciences, University of Oxford, South Parks Road, Oxford OX1 3RB, UK.
3
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
4
SUPA, School of Physics & Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh, EH9 3FD, UK dmarendu@ph.ed.ac.uk.

Abstract

Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green 'transcription factors' bind to cognate sites in strings of beads ('chromatin') to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster-red with red, green with green, but rarely red with green-to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent 'bridging-induced attraction' proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales.

PMID:
27060145
PMCID:
PMC4856988
DOI:
10.1093/nar/gkw135
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center