Polymer folding through active processes recreates features of genome organization
Name
goychuk-et-al-2023-polymer-folding-through-active-processes-recreates-features-of-genome-organization.pdf
Description
Published version
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17.16 MB
Format
Adobe PDF
Checksum (MD5)
7eac9e923251aee7675e4d7e1a635740
Author(s)
Goychuk, Andriy
Kannan, Deepti
Chakraborty, Arup K
Kardar, Mehran
Date Issued
May 16, 2023
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Citation
Goychuk, Andriy, Kannan, Deepti, Chakraborty, Arup K and Kardar, Mehran. 2023. "Polymer folding through active processes recreates features of genome organization." Proceedings of the National Academy of Sciences, 120 (20).
Version
Final published version
Abstract
From proteins to chromosomes, polymers fold into specific conformations that control their biological function. Polymer folding has long been studied with equilibrium thermodynamics, yet intracellular organization and regulation involve energy-consuming, active processes. Signatures of activity have been measured in the context of chromatin motion, which shows spatial correlations and enhanced subdiffusion only in the presence of adenosine triphosphate. Moreover, chromatin motion varies with genomic coordinate, pointing toward a heterogeneous pattern of active processes along the sequence. How do such patterns of activity affect the conformation of a polymer such as chromatin? We address this question by combining analytical theory and simulations to study a polymer subjected to sequence-dependent correlated active forces. Our analysis shows that a local increase in activity (larger active forces) can cause the polymer backbone to bend and expand, while less active segments straighten out and condense. Our simulations further predict that modest activity differences can drive compartmentalization of the polymer consistent with the patterns observed in chromosome conformation capture experiments. Moreover, segments of the polymer that show correlated active (sub)diffusion attract each other through effective long-ranged harmonic interactions, whereas anticorrelations lead to effective repulsions. Thus, our theory offers nonequilibrium mechanisms for forming genomic compartments, which cannot be distinguished from affinity-based folding using structural data alone. As a first step toward exploring whether active mechanisms contribute to shaping genome conformations, we discuss a data-driven approach.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Chemical Engineering
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution-NonCommercial-NoDerivs
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DOI of Published Version
https://doi.org/10.1073/pnas.2221726120
