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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 31, 2018 |
| Title |
A Zeb1 Hdac2 eNOS feedback circuitry identifies early cardiovascular precursors in naïve mouse embryonic stem cells (ChIP-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Soon after release from stemness, a relevant portion of mouse embryonic stem cells (mES), kept in naïve state by MEK inhibitor, GSK3 inhibitor and LIF (2i/L), expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes nitric oxide (NO). In this condition, an eNOS/NO-positive subpopulation (ESNO+) has been recognized by 4-amino-5-methylamino-2′,7′-difluorescein (DAF) fluorescence. Sorted ESNO+ cells expressed high levels of mesendodermal markers and efficiently generated cardiovascular precursors compared to eNOS/NO-negative cells (ESNO-). Mechanistically, the endogenous NO production deter- mined a rapid S-nitrosylation of Hdac2, a post-translational modification that compromised Hdac2 association with the transcription repression factor Zeb1. This condition destabilized Zeb1/chromatin interaction with genomic loci encoding for mesendodermal genes. Remarkably, Zeb1 or Hdac2 targeting activated an unscheduled transcription of mesendodermal lineage-associated genes in naïve mES revealing the Hdac2-Zeb1 pathway important for stemness maintenance in 2i/L. In contrast, eNOS targeting significantly reduced the endogenous NO production preventing the activation of mesendodermal gene transcription.
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| Overall design |
ChIP-Seq experiments of the Zeb1 transcription factor were performed three times on mouse embryonic stem cells (ES). One genomic input sample was generated for control purposes.
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| Contributor(s) |
Cencioni C, Spallotta F, Savoia M, Kuenne C, Guenther S, Re A, Wingert S, Rehage M, Sürün D, Siragusa M, Smith JG, Schnütgen F, von Melchner H, Rieger MA, Martelli F, Riccio A, Fleming I, Braun T, Zeiher AM, Farsetti A, Gaetano C |
| Citation(s) |
29599503 |
| Submission date |
Oct 05, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Carsten Kuenne |
| E-mail(s) |
Carsten.Kuenne@mpi-bn.mpg.de
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| Organization name |
Max Planck Institute for Heart and Lung Research
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| Department |
Bioinformatics
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| Street address |
Ludwigstrasse 43
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| City |
Bad Nauheim |
| ZIP/Postal code |
61231 |
| Country |
Germany |
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| Platforms (1) |
| GPL18635 |
Ion Torrent Proton (Mus musculus) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE104649 |
A Zeb1 Hdac2 eNOS feedback circuitry identifies early cardiovascular precursors in naïve mouse embryonic stem cells |
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| Relations |
| BioProject |
PRJNA413404 |
| SRA |
SRP119468 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE104646_peaks.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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