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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 19, 2021 |
| Title |
A cis-acting mechanism mediates trancriptional memory at Polycomb target genes in mammals [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Epigenetic inheritance of gene expression states enables a single genome to maintain distinct cellular identities. How histone modifications contribute to this process remains unclear. Using global chromatin perturbations and local, time-controlled modulation of transcription, we establish the existence of epigenetic memory of transcriptional activation for genes that can be silenced by the Polycomb group. This property emerges during cell differentiation and allows genes to be stably switched following a transient transcriptional stimulus. This transcriptional memory state at Polycomb targets operates in cis; however, rather than relying solely on read-and-write propagation of histone modifications, the memory is also linked to the strength of activating input opposing Polycomb proteins and therefore varies with the cellular context. Our data and computational simulations suggest a model whereby transcriptional memory arises from double-negative feedback between Polycomb-mediated silencing and active transcription. Epigenetic memory at Polycomb targets thus depends not only on histone modifications but also on the gene-regulatory network and underlying identity of a cell.
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| Overall design |
Transcriptomic analysis (RNA-seq) of mouse neural progenitor cells in untreated (2 replicates), PRC2-inhibitor-treated (2 replicates) and PRC2-inhibitor-washout (2 replicates) conditions (6 samples).
Transcriptomic analysis (RNA-seq) of mouse embryonic stem cells in untreated (2 replicates), PRC2-inhibitor-treated (2 replicates) and PRC2-inhibitor-washout (2 replicates) conditions (6 samples).
Transcriptomic analysis (RNA-seq) of immortalized mouse embryonic fibroblast line A (= C2) in wild-type (2 replicates), Ezh2 KO (2 replicates) and Ezh2 rescue (2 replicates) conditions (6 samples).
Transcriptomic analysis (RNA-seq) of immortalized mouse embryonic fibroblast line B (= C26) in wild-type (2 replicates), Ezh2 KO (2 replicates) and Ezh2 rescue (2 replicates) conditions (6 samples).
Nascent RNA analysis (chromosome-associated-RNA-seq) of immortalized mouse embryonic fibroblast line A (= C2) in wild-type (2 replicates), Ezh2 KO (2 replicates) and Ezh2 rescue (2 replicates) conditions (6 samples).
Nascent RNA analysis (chromosome-associated-RNA-seq) of immortalized mouse embryonic fibroblast line B (= C26) in wild-type (2 replicates), Ezh2 KO (2 replicates) and Ezh2 rescue (2 replicates) conditions (6 samples).
Transcriptomic analysis (RNA-seq) of immortalized mouse embryonic fibroblast line B bearing the DD-dCas9-VPR transgene and either sgRNAs targeting the Nr2f1 promoter, either before induction (2 replicates) or more than 9 days after the conclusion of a transient induction (2 replicates), or sgRNAs targeting the Foxa1 promoter, either before induction (2 replicates) or more than 9 days after the conclusion of a transient induction (2 replicates) (8 samples).
Targeted analysis (RNA-seq) of Nr2f1 mRNA levels in an equal mixture of RNA from wild-type immortalized mouse embryonic fibroblast line B cells in which Nr2f1 expression has been induced and RNA from Nr2f1-mutant cells in which Nr2f1 expression is repressed, or in an equal mixture of RNA from wild-type and Nr2f1-mutant cells in which Nr2f1 expression has been induced, or in RNA from each of two heterokaryon clones resulting from fusion of wild-type cells in which Nr2f1 expression has been induced and RNA from Nr2f1-mutant cells in which Nr2f1 expression is repressed, or in RNA from each of these two clones after dCas9-VPR-mediated induction of Nr2f1 expression, or in RNA from each of these two clones more than 9 days after the conclusion of such an induction, and targeted analysis of Foxa1 mRNA in a parallel series of conditions (16 samples).
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| Contributor(s) |
Holoch D, Wassef M, Lövkvist C, Zielinski D, Aflaki S, Lombard B, Héry T, Loew D, Howard M, Margueron R |
| Citation(s) |
34782763 |
| Submission date |
Mar 26, 2020 |
| Last update date |
Nov 18, 2021 |
| Contact name |
Daniel Holoch |
| E-mail(s) |
daniel.holoch@curie.fr
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| Phone |
0156246553
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| Organization name |
Institut Curie, Centre de Recherche
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| Department |
Genetics and Developmental Biology Unit
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| Lab |
Raphaël Margueron
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| Street address |
26 rue d'Ulm
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| City |
Paris |
| State/province |
Cedex 05 |
| ZIP/Postal code |
75248 |
| Country |
France |
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| Platforms (3) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (66)
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| This SubSeries is part of SuperSeries: |
| GSE147568 |
A cis-acting mechanism mediates trancriptional memory at Polycomb target genes in mammals |
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| Relations |
| BioProject |
PRJNA615388 |
| SRA |
SRP254116 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147563_RAW.tar |
49.4 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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