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| Status |
Public on Nov 16, 2020 |
| Title |
Morphine leads to global genome changes of H3K27me3 levels in mESCs by a self-regulatory mechanism of Polycomb Repressive Complex 2 (PRC2) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Environmentally induced epigenetic changes can lead to health problems or disease, but the mechanisms involved remain unclear. Morphine can pass through the placental barrier leading to abnormal embryo development. However, the mechanism by which morphine causes these effects and how the sometimes persist into the adulthood is not well known. To unravel the morphine-induced chromatin alterations involved in aberrant embryo development, we explore the role of H3K27me3/PRC2 repressive complex in gene expression and its transmission across cellular generations in response to morphine.
Using mouse embryonic stem cells as a model system, we find that chronic morphine treatment (24h) induces a global down-regulation of the histone modification H3K27me3. Conversely, ChIP-seq showed a remarkable increase in H3K27me3 levels at certain genomic sites, particularly promoters, disrupting selective target genes related to embryo development, cell cycle and metabolism. By a self-regulatory mechanism, transcription of components of the PRC2 complex responsible for H3K27me3 methylation, were consistently down-regulated by morphine, with high promoter levels of H3K27me3. Down-regulation of PRC2 components persisted for at least 48h (4 cell cycles) following morphine removal, though promoter H3K27me3 returned to control levels.
Morphine induces targeting of PRC2 complex to selected promoters, including those of PRC2 components, leading to characteristic changes in gene expression and global reduction in H3K27me3. Following morphine removal, enhanced promoter H3K227me3 levels revert to normal sooner than global H3K27me3 or transcript levels of PRC2 components. We suggest that H3K27me3 is involved in initiating morphine induced changes in gene expression but not in their maintenance.
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| Overall design |
Examination of one histone modification and transcriptomic profile in mESCs after morphine treatment.
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| Contributor(s) |
Muñoa-Hoyos I, Halsall JA, Ward C, Garcia I, Araolaza M, Urizar-Arenaza I, Gianzo M, Garcia P, Turner B, Subiran N |
| Citation(s) |
33168052 |
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| Submission date |
May 26, 2020 |
| Last update date |
Nov 16, 2020 |
| Contact name |
Iraia Maialen Muñoa Hoyos |
| E-mail(s) |
[email protected]
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| Organization name |
Universidad del País Vasco
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| Street address |
Barriso Sarriena S/N
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| City |
Leioa |
| State/province |
Bizkaia |
| ZIP/Postal code |
48940 |
| Country |
Spain |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA635171 |
| SRA |
SRP264846 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE151234_RAW.tar |
2.0 Gb |
(http)(custom) |
TAR (of BW, TXT) |
| GSE151234_Raw_counts_matrix_RNA-Seq.txt.gz |
3.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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