A unified-field theory of genome organization and gene regulation

Giuseppe Negro, Massimiliano Semeraro, Peter R. Cook*, Davide Marenduzzo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number111218
Pages (from-to)1-16
Number of pages16
JournaliScience
Volume27
Issue number12
Early online date22 Oct 2024
DOIs
Publication statusPublished - 20 Dec 2024

Keywords / Materials (for Non-textual outputs)

  • Biological sciences
  • Data processing in systems biology
  • Natural sciences
  • Systems biology

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