Design principles of 3D epigenetic memory systems
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Owen_accepted_withfigs.pdf
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35.84 MB
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Checksum (MD5)
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Author(s)
Owen, Jeremy A.
Osmanović, Dino
Mirny, Leonid
Date Issued
November 17, 2023
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Owen, Jeremy A., Osmanović, Dino and Mirny, Leonid. 2023. "Design principles of 3D epigenetic memory systems." Science, 382 (6672).
Version
Author's final manuscript
Abstract
Cells remember their identities, in part, by using epigenetic marks—chemical modifications placed along the genome. How can mark patterns remain stable over cell generations despite their constant erosion by replication and other processes? We developed a theoretical model that reveals that three-dimensional (3D) genome organization can stabilize epigenetic memory as long as (i) there is a large density difference between chromatin compartments, (ii) modifying “reader-writer” enzymes spread marks in three dimensions, and (iii) the enzymes are limited in abundance relative to their histone substrates. Analogous to an associative memory that encodes memory in neuronal connectivity, mark patterns are encoded in a 3D network of chromosomal contacts. Our model provides a unified account of diverse observations and reveals a key role of 3D genome organization in epigenetic memory.
Subjects
Multidisciplinary
MIT Department
Massachusetts Institute of Technology. Department of Physics
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1126/science.adg3053
