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.
| Original language | English |
|---|---|
| Article number | eadg3053 |
| Journal | Science |
| Volume | 382 |
| Issue number | 6672 |
| DOIs | |
| State | Published - 17 Nov 2023 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:Copyright © 2023 The Authors,
Funding
The authors are very grateful to M. Kardar for valuable scientific discussions. This research was funded by the National Human Genome Research Institute, NIH grant 3UM1HG011536 (L.M.); the National Institute of General Medical Sciences, NIH grant GM114190 (L.M.); and NSF award 2044895 (L.M.).
| Funders | Funder number |
|---|---|
| National Science Foundation | 2044895 |
| National Institutes of Health | 3UM1HG011536 |
| National Human Genome Research Institute | |
| National Institute of General Medical Sciences | GM114190 |