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| Status |
Public on Dec 31, 2012 |
| Title |
ZNF335 regulates stem cell proliferation and neuronal differentiation via Trithorax complex and REST/NRSF [gene expression] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The progression from stem cell to differentiated neuron is associated with extensive chromatin remodeling that controls gene expression, but the mechanisms that connect chromatin to gene expression are not well defined. Here we show that mutation of ZNF335 causes severe human microcephaly ("small brain"), small somatic size, and neonatal death. Germline Znf335 null mutations are embryonically lethal in mice, whereas RNA-interference studies and postmortem human studies show that Znf335 is essential for neural progenitor self-renewal, neurogenesis, and neuronal differentiation. Znf335 is a component of a vertebrate-specific, trithorax H3K4 methylation complex, while global ChIP-seq and mRNA expression studies show that Znf335 is a previously unsuspected, direct regulator of REST/NRSF, a master regulator of neural gene expression and neural cell fate, as well as other essential neural-specific genes. Our results reveal ZNF335 as an essential link between H3K4 complexes and REST/NRSF, and provide the first direct evidence that this pathway regulates human neurogenesis and neuronal differentiation.
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| Overall design |
ShRNA knockdown cells were FACS sorted and analyzed for changes in gene expression
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| |
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| Contributor(s) |
Yang YJ, Walsh CA |
| Citation(s) |
23178126 |
| |
| Submission date |
Mar 09, 2012 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Christopher A Walsh |
| Organization name |
Children's Hospital Boston
|
| Department |
Genetics
|
| Street address |
3 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE36386 |
ZNF335 regulates stem cell proliferation and neuronal differentiation via Trithorax complex and REST/NRSF |
|
| Relations |
| BioProject |
PRJNA163273 |
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