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| Status |
Public on Apr 08, 2020 |
| Title |
The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression to control neurite outgrowth [ChIP-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Cell type diversity during neuro-ectodermal (NE) differentiation is achieved through selective activation and silencing of neurodevelopmental genes. Here, we show a key role for the histone deacetylase complex MiDAC during neuronal differentiation of mouse embryonic stem cells (mESCs) into NE. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC mediates the removal of H4K20ac on the promoters and enhancers of pro-neural genes such as the axon guidance ligands Slit3 and Ntn1 while in parallel reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis thereby upregulating and inhibiting gene expression, respectively. Furthermore, neurite outgrowth defects in MiDAC KO neurons can be rescued by restoring Slit3/Robo3-Ntn1/Unc5b signaling. Taken together, our work suggests a crucial role for MiDAC in regulating the secretome of the Slit3/Robo3-Ntn1/Unc5b signaling axes to ensure the proper integrity of neurite development.
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| Overall design |
ChIP-seq was carried out in mESCs for the histone modification marks H3K4me1, H3K4me3, H3K27ac, H3K27me3 and for Dnttip1, a subunit of MiDAC. ChIPs against each histone mark or Dnttip1 were carried out at least in duplicate for each genotype. Genotypes used were WT, Dnttip1 KO and Elmsan1 KO.
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| Contributor(s) |
Mondal B, Jin H, Kallappagoudar S, Sedkov Y, Martinez T, Sentmanat MF, Poet GJ, Li C, Fan Y, Pruett-Miller SM, Herz H |
| Citation(s) |
32297854, 35820704 |
| |
| Submission date |
May 12, 2019 |
| Last update date |
Aug 02, 2022 |
| Contact name |
Hans-Martin Herz |
| E-mail(s) |
[email protected]
|
| Phone |
901-595-2058
|
| Organization name |
St. Jude Children's Research Hospital
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| Street address |
262 Danny Thomas Place
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105-3678 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (32)
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| This SubSeries is part of SuperSeries: |
| GSE131062 |
The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression to control neurite outgrowth |
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| Relations |
| BioProject |
PRJNA542516 |
| SRA |
SRP198174 |
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