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| Status |
Public on Aug 31, 2012 |
| Title |
Genome-wide mapping of Olig2 targets in primary oligodendrocytes |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Myelination by oligodendrocytes in the central nervous system (CNS) is essential for proper brain function, yet the molecular determinants that control this process remain poorly understood. The basic helix-loop-helix transcription factors Olig1 and Olig2 promote myelination, whereas bone morphogenetic protein (BMP) and Wnt/β-catenin signaling inhibit myelination. Here we show that these opposing regulators of myelination are functionally linked by the Olig1/2 common target Smad-interacting protein-1 (Sip1). We demonstrate that Sip1 is an essential modulator of CNS myelination. Sip1 represses differentiation inhibitory signals by antagonizing BMP receptor-activated Smad activity while activating crucial oligodendrocyte-promoting factors. Importantly, a key Sip1-activated target, Smad7, is required for oligodendrocyte differentiation and partially rescues differentiation defects caused by Sip1 loss. Smad7 promotes myelination by blocking the BMP- and β-catenin-negative regulatory pathways. Thus, our findings reveal that Sip1-mediated antagonism of inhibitory signaling is critical for promoting CNS myelination and point to new mediators for myelin repair.
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| Overall design |
ChIP-seq was performed to identify Olig2 direct target genes in oligodendrocytes during oligodendrocyte differentiation.
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| Contributor(s) |
Lu QR |
| Citation(s) |
22365546 |
| |
| Submission date |
Aug 30, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Qing Richard Lu |
| E-mail(s) |
QRichard.Lu@UTSouthwestern.edu
|
| Organization name |
UT southwestern medical center
|
| Street address |
5323 Harry Hines Boulevard
|
| City |
Dallas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (1) |
| GPL11282 |
Illumina Genome Analyzer (Rattus norvegicus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE40431 |
Dual-mode modulation of Smad signaling by Smad-interacting protein Sip1 is required for myelination in the central nervous system |
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| Relations |
| BioProject |
PRJNA174195 |
| SRA |
SRP015333 |
