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This content will become publicly available on August 1, 2025

Title: Mapping the dynamics of epigenetic adaptation in S. pombe during heterochromatin misregulation
Epigenetic mechanisms enable cells to develop novel adaptive phenotypes without altering their genetic blueprint. Recent studies show histone modifications, such as heterochromatin-defining H3K9 methylation (H3K9me), can be redistributed to establish adaptive phenotypes. We developed a precision-engineered genetic approach to trigger heterochromatin misregulation on-demand in fission yeast. This enabled us to trace genome-scale RNA and H3K9me changes over time in long-term, continuous cultures. Adaptive H3K9me establishes over remarkably slow timescales relative to the initiating stress. We captured dynamic H3K9me redistribution events which depend on an RNA binding complex MTREC, ultimately leading to cells converging on an optimal adaptive solution. Upon stress removal, cells relax to new transcriptional and chromatin states, establishing memory that is tunable and primed for future adaptive epigenetic responses. Collectively, we identify the slow kinetics of epigenetic adaptation that allow cells to discover and heritably encode novel adaptive solutions, with implications for drug resistance and response to infection.  more » « less
Award ID(s):
2316281
PAR ID:
10538520
Author(s) / Creator(s):
; ; ; ; ; ; ; ;
Publisher / Repository:
Developmental Cell
Date Published:
Journal Name:
Developmental Cell
Volume:
59
Issue:
16
ISSN:
1534-5807
Page Range / eLocation ID:
2222 to 2238.e4
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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