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| Status |
Public on Aug 22, 2018 |
| Title |
Chd5 regulates a ribosome biogenesis switch controlling neural cell fate specification |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Cell fate specification of neural stem/progenitor cells (NSCs) is an intricate developmental process that determines neural cell identity. While transcriptional mechanisms undoubtedly affect this process, translational mechanisms are much less understood. Here we show that deficiency of the chromatin remodeler Chromodomain Helicase DNA binding protein 5 (Chd5) causes transcriptional de-repression of multiple ribosomal subunit genes, increases protein synthesis, and expands the activated stem cell pool leading to perturbation of NSC fate. Compromised H3K27me3 in Chd5 deficient NSCs during early cell fate specification underlies the generation of excessive astrocytes at the expense of neurons at later stages of differentiation. Chd5 expression rescues these cell fate defects while simultaneously reestablishing H3K27me3, and inhibition of the H3K27me3-specific demethylase Utx restores appropriate cell fate specification in NSCs lacking Chd5. These findings define a Chd5-Utx-H3K27me3 axis pivotal in ribosome biogenesis and translation during neurogenesis, consistent with compromised CHD5 being implicated in glioma.
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| |
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| Overall design |
mRNA profiles of primary neural/stem progenitor cells (NSCs) of wild type (+/+) and Chd5-/- mice were generated, in duplicate, using Illumina NextSeq 500.
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| |
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| Contributor(s) |
Mills AA, Hwang D |
| Citation(s) |
30456361 |
| |
| Submission date |
Apr 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Dong-Woo Hwang |
| E-mail(s) |
[email protected]
|
| Phone |
(516) 367-8349
|
| Organization name |
Cold Spring Harbor Laboratory
|
| Department |
Cancer Center
|
| Lab |
Alea A. Mills
|
| Street address |
1 Bungtown Rd
|
| City |
Cold Spring Harbor |
| State/province |
NY |
| ZIP/Postal code |
11724 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA319371 |
| SRA |
SRP073725 |
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