3D polymer simulations of genome organization and transcription across different chromosomes and cell types

TL;DR

This paper uses 3D polymer simulations to model human genome organization and transcription, demonstrating how structural and external factors influence transcriptional activity across different chromosomes and cell types.

Contribution

It introduces a diffusing transcription factors model that accurately predicts transcriptional activity and chromatin conformations in various human cell lines.

Findings

Simulation reveals pathways to regulate transcription via structural or external factors.

Model predictions align with GRO-seq experimental data.

Transcriptional activity can be controlled by chromatin structure or transcription factor levels.

Abstract

We employ the diffusing transcription factors model for numerical simulation of chromatin topology conformations and transcriptional processes of human chromatin. Simulations of a short chromatin filament reveal different possible pathways to regulate transcription: it is shown that the transcriptional activity profile can be regulated and controlled by either acting on the chain structural properties, or on external factors, such as the number of transcription factors. Additionally, comparisons between GRO-seq experimental data and large scale numerical simulation of entire chromosomes from the human umbilical vein endothelial cell and the B-lmphocyte GM12878 show that the model provides reliable and statistically significant predictions for transcription across different cell-lines.