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Activation of Clustered IFNγ Target Genes Drives Cohesin-Controlled Transcriptional Memory.

Authors :
Siwek W
Tehrani SSH
Mata JF
Jansen LET
Source :
Molecular cell [Mol Cell] 2020 Nov 05; Vol. 80 (3), pp. 396-409.e6. Date of Electronic Publication: 2020 Oct 26.
Publication Year :
2020

Abstract

Cytokine activation of cells induces gene networks involved in inflammation and immunity. Transient gene activation can have a lasting effect even in the absence of ongoing transcription, known as long-term transcriptional memory. Here we explore the nature of the establishment and maintenance of interferon γ (IFNγ)-induced priming of human cells. We find that, although ongoing transcription and local chromatin signatures are short-lived, the IFNγ-primed state stably propagates through at least 14 cell division cycles. Single-cell analysis reveals that memory is manifested by an increased probability of primed cells to engage in target gene expression, correlating with the strength of initial gene activation. Further, we find that strongly memorized genes tend to reside in genomic clusters and that long-term memory of these genes is locally restricted by cohesin. We define the duration, stochastic nature, and molecular mechanisms of IFNγ-induced transcriptional memory, relevant to understanding enhanced innate immune signaling.<br />Competing Interests: Declaration of Interests The authors declare no competing interests.<br /> (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1097-4164
Volume :
80
Issue :
3
Database :
MEDLINE
Journal :
Molecular cell
Publication Type :
Academic Journal
Accession number :
33108759
Full Text :
https://doi.org/10.1016/j.molcel.2020.10.005