Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models

TL;DR

This paper introduces a polymer modeling approach to predict 3D chromatin organization in mammalian genomes, integrating bioinformatic data and experimental validation to understand chromosome architecture.

Contribution

The study presents a novel polymer model that predicts chromatin interactions from protein binding sites, linking population data to single-cell organization.

Findings

Model accurately predicts chromatin interactions

FISH experiments validate the model

Reveals diverse 3D conformations

Abstract

The three-dimensional organisation of chromosomes can be probed using methods such as Capture-C. However it is unclear how such population level data relates to the organisation within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modelling scheme based on the assumption that chromosome architecture is maintained by protein bridges which form chromatin loops. To test the model we perform FISH experiments and also compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations.