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Status |
Public on Nov 22, 2024 |
Title |
A histone hyperacetylation pulse induces cellular memory of gene expression and 3-dimensional genome folding [ATAC-seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Epigenetic memory enables the stable propagation of gene expression patterns in response to transient developmental and environmental stimuli. Although 3-dimensional (3D) organisation is emerging as a key regulator of genome function due its role in gene expression control, it is unknown whether it contributes to cellular memory. Here, we establish that acute perturbation of the epigenome can induce cellular memory of gene expression in mouse embryonic stem cells (mESCs). Specifically, we uncover how a pulse of histone deacetylase inhibition translates to changes in the histone acetylation and methylation landscape, as well as global and local genome folding. While most epigenomic and transcriptional changes are readily reversible once the perturbation is removed, architectural features are not fully reestablished. Upon a second transient pulse of hyperacetylation, hundreds of genes maintain their dysregulated state. Using ultra-deep Micro-C, we associate memory of gene expression with enhancer-promoter contacts and repressive chromatin topology mediated by Polycomb. These results uncover the complex interplay between different epigenetic regulatory layers and establish a novel link between genome folding and cellular memory.
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Overall design |
Micro-C experiments in mouse ESCs in control (DMSO), TSA-treated or 24-hour recovery (REC) conditions.
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Web link |
https://doi.org/10.1101/2024.11.21.624660
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Contributor(s) |
Paldi F, Szalay M, Di Stefano M, Cavalli G |
Citation missing |
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BioProject |
PRJNA1117356 |
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Submission date |
Oct 28, 2024 |
Last update date |
Nov 26, 2024 |
Contact name |
Marco Di Stefano |
E-mail(s) |
[email protected]
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Organization name |
Institut de Génétique Humaine - CNRS / University of Edinburgh
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Lab |
Giacomo Cavalli lab
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Street address |
141 rue de la Cardonille
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City |
Montpellier |
ZIP/Postal code |
34396 |
Country |
France |
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Platforms (1) |
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Samples (6)
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GSM8599123 |
ATAC-seq mESC TSA-treated replicate 2 |
GSM8599124 |
ATAC-seq mESC 24h recovery after TSA washout replicate 1 |
GSM8599125 |
ATAC-seq mESC 24h recovery after TSA washout replicate 2 |
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This SubSeries is part of SuperSeries: |
GSE281151 |
Transient histone deacetylase inhibition induces cellular memory of gene expression and three-dimensional genome folding |
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