A polymer model for prediction of 3D structure and transcriptional activity of human chromosomes

A multicolour polymer model facilitating prediction of 3D structure and transcriptional activity of human chromosomes
Giuseppe Negro - Università degli studi di Bari and INFN
Young Seminars SIFS
Abstract: Within each human cell, different kinds of RNA polymerases and a panoply of transcription factors bind chromatin to simultaneously determine 3D chromosome structure and transcriptional programme. Experiments show that, in some cases, different proteins segregate to form specialised transcription factories; in others they mix together, binding promiscuously the same chromatin stretch. We use molecular dynamics simulations to study a polymer model for chromosomes accounting for multiple types (“colours”) of chromatin-binding proteins. Our multi-colour model shows the spontaneous emergence of both segregated and mixed clusters of chromatin-bound proteins, depending mainly on their size, thereby reconciling the previous experimental observations. Additionally, the model leads to non-trivial spatio-temporal correlations between different transcription units, dependent on the underlying chromosome structure. Small-world networks emerge; in these, positive and negative correlations in activities of transcription units provide simple explanations of why adjacent units in large domains are co-transcribed so often. We also explain how local genome edits induce distant omnigenic and pangenomic effects, and develop ways to predict activities of all transcription units on human chromosomes.
[1] 3D polymer simulations of genome organisation and transcription across different chromosomes and cell types. M Semeraro, G Negro, A Suma, G Gonnella, D Marenduzzo. Physica A: Statistical Mechanics and its Applications 625, 129013, (2023).
[2] A unified-field theory of genome organization and gene regulation. G. Negro, M. Semeraro, P. R. Cook, D. Marenduzzo. arXiv preprint arXiv:2308.02861 (2023).
[3] A multicolour polymer model for the prediction of 3D structure and transcription in human chromatin. M. Semeraro, G. Negro, A. Suma, G. Gonnella, P. R. Cook, D. Marenduzzo bioRxiv 2023.01.16.524198, (2023).
www.fisicastat...