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Activation of Clustered IFNγ Target Genes Drives Cohesin-Controlled Transcriptional Memory.
- 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.)
- Subjects :
- Cell Cycle Proteins physiology
Cell Line
Chromatin genetics
Chromosomal Proteins, Non-Histone physiology
Gene Expression Regulation immunology
HeLa Cells
Humans
Inflammation
Interferon-gamma physiology
Protein Binding genetics
STAT1 Transcription Factor metabolism
Signal Transduction genetics
Transcription, Genetic genetics
Transcriptional Activation physiology
Cohesins
Cell Cycle Proteins metabolism
Chromosomal Proteins, Non-Histone metabolism
Interferon-gamma metabolism
Transcriptional Activation genetics
Subjects
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