Work

Modelling transcriptional silencing and its coupling to 3D genome organisation

Year: 2025

Type: article

Abstract: transcriptional activators has been extensively investigated, gene silencing remains understudied, especially by modelling. This study employs 3D simulations to study the biophysics of a chromatin fibre where active transcription factors compete with repressors for binding to transcription units along the fibre, and investigates how different silencing mechanisms affect 3D chromatin structure and transcription. We examine three gene silencing feedback mechanisms: positive, negative, and neutral. These mechanisms capture different silencing pathways observed or proposed in biological systems. Our findings reveal that, whilst all mechanisms lead to a silencing transition, the signatures of this transition depend on the choice of the feedback. The latter controls the morphologies of the emergent 3D transcription factor clusters, the average gene expression and its variability, or gene noise, and the network of ensuing correlations between activities of neighbouring transcription units. These results provide insights into the biophysics of gene silencing, as well as into the interplay between transcriptional regulation and 3D genome organisation.

Source: Soft Matter

DOI: 10.1039/d5sm00686d

Authors: M. Semeraro, G. Negro, D. Marenduzzo, G. Forte

Institutions: Istituto Nazionale di Fisica Nucleare, Sezione di Bari, University of Bari Aldo Moro, University of Edinburgh

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: Wellcome Trust, Leverhulme Trust

Awards: Understanding the mechanistic relationship between 3D gene structure and transcription, G8173813908