Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization

Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem c...

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Bibliographic Details
Published in:Nature communications 2024-06, Vol.15 (1), p.5393-15, Article 5393
Main Authors: Salari, Hossein, Fourel, Geneviève, Jost, Daniel
Format: Article
Language:English
Subjects:
631/337/103
631/337/386
631/337/572
631/57/2266
639/766/747
Animals
Chromosomes
Chromosomes - chemistry
Cohesin
Cohesins - metabolism
Conformation
Data analysis
Embryo cells
Embryogenesis
Embryonic Stem Cells
Folding
Gene Expression Regulation
Genes
Heterochromatin
Heterochromatin - metabolism
Humanities and Social Sciences
Life Sciences
Mice
multidisciplinary
Polymers
RNA Polymerase II - metabolism
Science
Science (multidisciplinary)
Stem cells
Stochastic Processes
Transcription
Transcription factors
Transcription, Genetic
Valency
Citations: Items that this one cites
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Summary:Although our understanding of the involvement of heterochromatin architectural factors in shaping nuclear organization is improving, there is still ongoing debate regarding the role of active genes in this process. In this study, we utilize publicly-available Micro-C data from mouse embryonic stem cells to investigate the relationship between gene transcription and 3D gene folding. Our analysis uncovers a nonmonotonic - globally positive - correlation between intragenic contact density and Pol II occupancy, independent of cohesin-based loop extrusion. Through the development of a biophysical model integrating the role of transcription dynamics within a polymer model of chromosome organization, we demonstrate that Pol II-mediated attractive interactions with limited valency between transcribed regions yield quantitative predictions consistent with chromosome-conformation-capture and live-imaging experiments. Our work provides compelling evidence that transcriptional activity shapes the 4D genome through Pol II-mediated micro-compartmentalization. Here, the authors explore gene transcription’s impact on 3D gene folding. Combining experimental data analysis and biophysical modeling, they suggest Pol II-mediated interactions shapes intra-gene condensation and inter-gene contacts and impacts gene dynamics.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-49727-7