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Epigenetics Chromatin. 2016 Dec 24;9:57. doi: 10.1186/s13072-016-0093-1. eCollection 2016.

Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells.

Author information

1
Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
2
Biophysical Genomics Group, Department of Cell Biology and Genetics, Erasmus Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
3
Research Group Genome Organization and Function, Deutsches Krebsforschungszentrum (DKFZ) & BioQuant, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Abstract

BACKGROUND:

Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is unclear how domain plasticity modulates genomic accessibility for soluble factors.

RESULTS:

Here, we combine and compare a high-resolution topology analysis of interacting chromatin loci with fluorescence correlation spectroscopy measurements of domain dynamics in single living cells. We identify topologically and dynamically independent chromatin domains of ~1 Mb in size that are best described by a loop-cluster polymer model. Hydrodynamic relaxation times and gyration radii of domains are larger for open (161 ± 15 ms, 297 ± 9 nm) than for dense chromatin (88 ± 7 ms, 243 ± 6 nm) and increase globally upon chromatin hyperacetylation or ATP depletion.

CONCLUSIONS:

Based on the domain structure and dynamics measurements, we propose a loop-cluster model for chromatin domains. It suggests that the regulation of chromatin accessibility for soluble factors displays a significantly stronger dependence on factor concentration than search processes within a static network.

KEYWORDS:

Chromatin conformation capture carbon copy (5C); Chromatin structure; Fluorescence correlation spectroscopy (FCS); Polymer model; Quantitative microscopy; Targeted chromatin capture (T2C)

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