Abstract
Understanding the structure of interphase chromosomes is essential to elucidate regulatory mechanisms of gene expression. During recent years, high-throughput DNA sequencing expanded the power of chromosome conformation capture (3C) methods that provide information about reciprocal spatial proximity of chromosomal loci. Since 2012, it is known that entire chromatin in interphase chromosomes is organized into regions with strongly increased frequency of internal contacts. These regions, with the average size of ∼1 Mb, were named topological domains. More recent studies demonstrated presence of unconstrained supercoiling in interphase chromosomes. Using Brownian dynamics simulations, we show here that by including supercoiling into models of topological domains one can reproduce and thus provide possible explanations of several experimentally observed characteristics of interphase chromosomes, such as their complex contact maps.
Highlights
Several recent papers have shown that chromatin fibres in interphase chromosomes are organized into $1 Mb large domains that can be seen on 3C contact maps as sharply delimited regions with highly increased frequency of internal contacts [1,2,3,4]
We further assumed that this attachment limits the possibility of axial rotation of chromatin fibres, the anchoring nuclear granules are essentially free to move within the nucleus
In the model that we propose here, border elements of a given topological domains are not enforced to be in a contact
Summary
Several recent papers have shown that chromatin fibres in interphase chromosomes are organized into $1 Mb large domains that can be seen on 3C contact maps as sharply delimited regions with highly increased frequency of internal contacts [1,2,3,4]. Chromatin stretches forming individual topological domain fold into segregated globules Once such globules are formed and maintained, the contacts between fluctuating segments of the same globule are expected to be much more frequent than contacts between segments belonging to two neighbouring, but segregated, domains. In a more recent modelling study, Barbieri et al [6] proposed that separate globules can form by interaction with polyvalent binders that only bind within a given topological domain. Barbieri et al [6] did not propose though what could be these specific binders
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