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

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

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).