Epigenetic inheritance of gene silencing is maintained by a self-tuning mechanism based on resource competition
File(s)
Published version
Author(s)
Karin, Omer
Miska, Eric A
Simons, Benjamin D
Type
Journal Article
Abstract
Biological systems can maintain memories over long timescales, with examples including memories in the brain and immune system. It is unknown how functional properties of memory systems, such as memory persistence, can be established by biological circuits. To address this question, we focus on transgenerational epigenetic inheritance in Caenorhabditis elegans. In response to a trigger, worms silence a target gene for multiple generations, resisting strong dilution due to growth and reproduction. Silencing may also be maintained indefinitely upon selection according to silencing levels. We show that these properties imply the fine-tuning of biochemical rates in which the silencing system is positioned near the transition to bistability. We demonstrate that this behavior is consistent with a generic mechanism based on competition for synthesis resources, which leads to self-organization around a critical state with broad silencing timescales. The theory makes distinct predictions and offers insights into the design principles of long-term memory systems.
Date Issued
2023-01-18
Date Acceptance
2022-12-12
Citation
Cell Systems, 2023, 14 (1), pp.24-40
ISSN
2405-4720
Publisher
Elsevier (Cell Press)
Start Page
24
End Page
40
Journal / Book Title
Cell Systems
Volume
14
Issue
1
Copyright Statement
© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000961084900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Biochemistry & Molecular Biology
BISTABILITY
Cell Biology
DURATION
functional benefits
gene ON
GERMLINE
HOMEOSTASIS
Life Sciences & Biomedicine
MEMORY
PATHWAYS
PIRNAS
ROBUST PERFECT ADAPTATION
Science & Technology
SMALL RNA INHERITANCE
stochastic silencing
TRANSGENERATIONAL INHERITANCE
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2023-01-18