Abstract

The DEK oncoprotein is a ubiquitous nuclear factor that has been consistently associated with tumor progression: its expression level differs between normal and cancer cells, raising the possibility of using DEK as a tumor marker. Moreover, DEK is a non-histone architectural chromatin factor that may influence nucleosomal accessibility and therefore gene activity. The interest of this work is to investigate, using super-resolution microscopy approaches, the correlation between the organization of the DEK oncoprotein and the local chromatin structure depending on the degree of cell malignancy.

Highlights

  • Chromatin folding and interactions play essential roles in fundamental processes such as regulation of gene expression and cellular specialization

  • We introduce a polymer model to study the organization of the diploid human genome: it is data-driven as all parameters can be derived from high-throughput chromosome conformation capture (Hi-C) data; it is a mechanistic model since the energy function is explicitly written out based on a few biologically motivated hypotheses

  • While Hi-C measurements often detect numerous interactions (108), our previous results showed that only 2-9% of Hi-C interactions, which we call specific interactions, are required to generate ensembles of 3D single-cell chromatin conformations that collectively exhibit the observed Hi-C contact patterns

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Summary

Introduction

Chromatin folding and interactions play essential roles in fundamental processes such as regulation of gene expression and cellular specialization. We describe the self-attracting polymer chain as a liquid droplet and study the transitions between different types of chromatin organization at the mesoscale as a function of the droplet surface tension, the LAD fraction of the chromatin, and their interaction strength with the nuclear lamina. 1542-Pos Data-Driven Polymer Model for Mechanistic Exploration of Diploid Genome Organization Bin Zhang.

Results
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