Work

A unified-field theory of genome organization and gene regulation

Year: 2024

Type: article

Abstract: Our aim is to predict how often genic and non-genic promoters fire within a cell. We first review a parsimonious pan-genomic model for genome organization and gene regulation, where transcription rate is determined by proximity in 3D space of promoters to clusters containing appropriate factors and RNA polymerases. This model reconciles conflicting results indicating that regulatory mammalian networks are both simple (as over-expressing just 4 transcription factors switches cell state) and complex (as genome-wide association studies show phenotypes like cell type are determined by thousands of loci rarely encoding such factors). We then present 3D polymer simulations, and a proximity formula based on our biological model that enables prediction of transcriptional activities of all promoters in three human cell types. This simple fitting-free formula contains just one variable (distance on the genetic map to the nearest active promoter), and we suggest it can in principle be applied to any organism.

Source: iScience

DOI: 10.1016/j.isci.2024.111218

Authors: Giuseppe Negro, Massimiliano Semeraro, Peter R. Cook, Davide Marenduzzo

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

Language: English

Topic: Genomics and Chromatin Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,150

Funders: Wellcome Trust, Ministero dell’Istruzione, dell’Università e della Ricerca, European Research Council