title: Diffusion-driven looping provides a consistent framework for chromatin organization.
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.
authors.affiliation: Institute for Theoretical Physics, Heidelberg University, Heidelberg, Germany. bohn@tphys.uni-heidelberg.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Bohn
authors.forename: Dieter W
authors.initials: DW
authors.lastname: Heermann
mesh_terms: D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004058:Diffusion; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011108:Polymers / Q000737:chemistry / Q000378:metabolism
chemical_list: D002843:Chromatin; D011108:Polymers
references.citation: Biophys J. 2001 Apr;80(4):1940-56
references.pmid: 11259307
references.citation: Biochem J. 2001 Jun 1;356(Pt 2):297-310
references.pmid: 11368755
references.citation: Genes Dev. 2003 Oct 1;17(19):2406-20
references.pmid: 14522946
references.citation: J Mol Biol. 1999 Jan 22;285(3):1053-65
references.pmid: 9887267
references.citation: Curr Opin Genet Dev. 2007 Oct;17(5):408-14
references.pmid: 17913490
references.citation: J Cell Biol. 1996 Dec;135(6 Pt 1):1427-40
references.pmid: 8978813
references.citation: J Chem Phys. 2009 May 7;130(17):174901
references.pmid: 19425810
references.citation: Int Rev Cytol. 2005;242:283-336
references.pmid: 15598472
references.citation: PLoS Biol. 2005 May;3(5):e157
references.pmid: 15839726
references.citation: Mol Biol Cell. 2004 Dec;15(12):5678-92
references.pmid: 15371546
references.citation: PLoS Comput Biol. 2008 Aug 22;4(8):e1000153
references.pmid: 18725929
references.citation: Nat Genet. 2002 Nov;32(3):347-52
references.pmid: 12410231
references.citation: Science. 2009 Oct 9;326(5950):289-93
references.pmid: 19815776
references.citation: Phys Biol. 2009 Jul 01;6(2):025008
references.pmid: 19571359
references.citation: Genome Res. 2003 Sep;13(9):1998-2004
references.pmid: 12915492
references.citation: Curr Opin Genet Dev. 2006 Oct;16(5):490-5
references.pmid: 16904310
references.citation: Cell. 2009 Jun 26;137(7):1194-211
references.pmid: 19563753
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10548-55
references.pmid: 8855215
references.citation: Nat Genet. 2006 Nov;38(11):1348-54
references.pmid: 17033623
references.citation: J Cell Biol. 1995 Sep;130(6):1239-49
references.pmid: 7559748
references.citation: Nature. 2007 Jan 25;445(7126):379-781
references.pmid: 17251970
references.citation: Eur Phys J E Soft Matter. 2006 Mar;19(3):241-9
references.pmid: 16547610
references.citation: Mol Cell. 2002 Dec;10(6):1453-65
references.pmid: 12504019
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16495-500
references.pmid: 15545610
references.citation: Cell. 2004 Mar 5;116(5):683-98
references.pmid: 15006351
references.citation: Chromosome Res. 2003;11(5):435-45
references.pmid: 12971720
references.citation: Exp Cell Res. 2004 Dec 10;301(2):266-79
references.pmid: 15530862
references.citation: Biophys J. 2009 Oct 21;97(8):2146-53
references.pmid: 19843447
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2007 Nov;76(5 Pt 1):051805
references.pmid: 18233679
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3812-7
references.pmid: 19234129
references.citation: Nat Rev Genet. 2001 Apr;2(4):292-301
references.pmid: 11283701
references.citation: Trends Biochem Sci. 2003 Jun;28(6):277-80
references.pmid: 12826398
references.citation: J Cell Biol. 2009 Sep 21;186(6):825-34
references.pmid: 19752020
references.citation: Mol Cell Biol. 2007 Jun;27(12):4475-87
references.pmid: 17420274
references.citation: J Chem Phys. 2010 Jan 28;132(4):044904
references.pmid: 20113063
references.citation: Nucleic Acids Res. 2009 Jun;37(11):3558-68
references.pmid: 19359359
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2008 Jun;77(6 Pt 1):061923
references.pmid: 18643316
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2710-4
references.pmid: 7708711
references.citation: J Cell Biol. 1984 Jul;99(1 Pt 1):42-52
references.pmid: 6736132
references.citation: Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1996 May;53(5):5063-5074
references.pmid: 9964837
references.citation: Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7854-8
references.pmid: 8356094
references.citation: Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 2000 Apr;61(4 Pt B):4078-89
references.pmid: 11088200
references.citation: Biophys J. 1994 Mar;66(3 Pt 1):827-37
references.pmid: 8011915
references.citation: J Cell Biol. 2004 Sep 13;166(6):815-25
references.pmid: 15364959
references.citation: J Cell Biol. 1994 Apr;125(1):1-10
references.pmid: 8138564
references.citation: Chromosome Res. 2007;15(7):899-916
references.pmid: 17926137
references.citation: Trends Cell Biol. 2001 Jun;11(6):250-7
references.pmid: 11356361
references.citation: PLoS Biol. 2006 May;4(5):e138
references.pmid: 16623600
references.citation: Science. 2002 Feb 15;295(5558):1306-11
references.pmid: 11847345
references.citation: Trends Genet. 2007 Mar;23(3):126-33
references.pmid: 17280735
references.citation: J Cell Sci. 2004 Sep 1;117(Pt 19):4603-14
references.pmid: 15331668
references.citation: Nature. 2006 Jun 8;441(7094):770-3
references.pmid: 16760982
references.citation: Cell. 2008 Apr 18;133(2):265-79
references.pmid: 18423198