A Dynamical Model Reveals Gene Co-Localizations in Nucleus

TL;DR

This paper presents a dynamical model based on fractional Brownian motion to explain gene co-localization in the nucleus, highlighting the roles of transcription factors and gene mobility in gene expression regulation.

Contribution

It introduces a novel dynamical model incorporating sub-diffusion to better match experimental chromatin movement data and explains gene co-localization without direct interactions.

Findings

Preferential gene co-localization can occur without direct interactions.

Fractional Brownian motion models gene mobility more accurately.

Increasing transcription factors decreases gene co-localization.

Abstract

Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency- or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes.