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| Status |
Public on Jun 15, 2023 |
| Title |
Symmetric inheritance of parental histones governs epigenome maintenance and stem cell identity [RNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Modified parental histones are segregated symmetrically to daughter DNA strands during replication and inherited through mitosis. How this may sustain the epigenome and cell identity remains unknown. Here, we show that transmission of histone-based information during replication maintains epigenome fidelity and embryonic stem cell plasticity. Asymmetric segregation of parental histones H3-H4 in MCM2-2A mutants compromised mitotic inheritance of histone modifications and globally altered the epigenome. This included widespread spurious deposition of repressive modifications, suggesting elevated epigenetic noise. Moreover, H3K9me3 loss at repeats caused de-repression and H3K27me3 redistribution across bivalent promoters correlated with misexpression of developmental genes. MCM2-2A mutation challenged dynamic transitions in cellular states across the cell cycle, enhancing naïve pluripotency and reducing lineage priming in G1. Further, developmental competence was diminished, correlating with impaired exit from pluripotency. Collectively, this argues that epigenetic inheritance of histone modifications maintains a correctly balanced and dynamic chromatin landscape able to support mammalian differentiation.
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| Overall design |
Total RNA-seq of 8 WT vs. 8 MCM2-2A clones (2-6 replicates each; rRNA-depleted) and WT vs.3 POLE4-KO clones (3 biological replicates each; rRNA-depleted). Rescue experiment including WT, MCM2-2A and the corresponding MCM2-R in which the mutation was reverted (4 biological replicates; rRNA-depleted). Additional sample information can be found in Supplementary Table 1
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| Contributor(s) |
Wenger A, Biran A, Alcaraz N, Redó-Riveiro A, Sell AC, Krautz R, Flury V, Reverón-Gómez N, Solis-Mezarino V, Völker-Albert M, Imhof A, Andersson R, Brickman JM, Groth A |
| Citation(s) |
37666988 |
| |
| Submission date |
Jul 14, 2020 |
| Last update date |
Sep 14, 2023 |
| Contact name |
Anja Groth |
| E-mail(s) |
[email protected]
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| Organization name |
Novo Nordisk Foundation Center for Protein Research
|
| Street address |
Blegdamsvej 3B
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| City |
Copenhagen |
| ZIP/Postal code |
2200 |
| Country |
Denmark |
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| Platforms (2) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
| GPL30172 |
NextSeq 2000 (Mus musculus) |
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| Samples (68)
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| This SubSeries is part of SuperSeries: |
| GSE154391 |
Symmetric inheritance of parental histones governs epigenome maintenance and stem cell identity |
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| Relations |
| BioProject |
PRJNA646124 |
| SRA |
SRP271754 |
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