title: Spatially confined folding of chromatin in the interphase nucleus.
abstract: Genome function in higher eukaryotes involves major changes in the spatial organization of the chromatin fiber. Nevertheless, our understanding of chromatin folding is remarkably limited. Polymer models have been used to describe chromatin folding. However, none of the proposed models gives a satisfactory explanation of experimental data. In particularly, they ignore that each chromosome occupies a confined space, i.e., the chromosome territory. Here, we present a polymer model that is able to describe key properties of chromatin over length scales ranging from 0.5 to 75 Mb. This random loop (RL) model assumes a self-avoiding random walk folding of the polymer backbone and defines a probability P for 2 monomers to interact, creating loops of a broad size range. Model predictions are compared with systematic measurements of chromatin folding of the q-arms of chromosomes 1 and 11. The RL model can explain our observed data and suggests that on the tens-of-megabases length scale P is small, i.e., 10-30 loops per 100 Mb. This is sufficient to enforce folding inside the confined space of a chromosome territory. On the 0.5- to 3-Mb length scale chromatin compaction differs in different subchromosomal domains. This aspect of chromatin structure is incorporated in the RL model by introducing heterogeneity along the fiber contour length due to different local looping probabilities. The RL model creates a quantitative and predictive framework for the identification of nuclear components that are responsible for chromatin-chromatin interactions and determine the 3-dimensional organization of the chromatin fiber.
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands.
authors.forename: Julio
authors.initials: J
authors.lastname: Mateos-Langerak
authors.forename: Manfred
authors.initials: M
authors.lastname: Bohn
authors.forename: Wim
authors.initials: W
authors.lastname: de Leeuw
authors.forename: Osdilly
authors.initials: O
authors.lastname: Giromus
authors.forename: Erik M M
authors.initials: EM
authors.lastname: Manders
authors.forename: Pernette J
authors.initials: PJ
authors.lastname: Verschure
authors.forename: Mireille H G
authors.initials: MH
authors.lastname: Indemans
authors.forename: Hinco J
authors.initials: HJ
authors.lastname: Gierman
authors.forename: Dieter W
authors.initials: DW
authors.lastname: Heermann
authors.forename: Roel
authors.initials: R
authors.lastname: van Driel
authors.forename: Sandra
authors.initials: S
authors.lastname: Goetze
mesh_terms: D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry*; D005260:Female; D005347:Fibroblasts / Q000166:cytology*; D006801:Humans; D007399:Interphase; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D002843:Chromatin