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| Status |
Public on Feb 11, 2018 |
| Title |
A Histone Deacetylase 3-Dependent Pathway Delimits Peripheral Myelin Growth and Functional Regeneration [ChIP-Seq] |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Schwann cell remyelination defects impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms that mediate remyelination block remain elusive. Upon small-molecule epigenetic screening, we identified HDAC3, a histone-modifying enzyme, as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 markedly enhances myelin growth and regeneration, and improves functional recovery after peripheral nerve injury. HDAC3 antagonizes myelinogenic neuregulin/PI3K/AKT signaling axis. Moreover, genome-wide profiling analyses reveal that HDAC3 represses pro-myelinating programs through epigenetic silencing, while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann-cell-specific deletion of either Hdac3 or Tead4 results in a profound increase in myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3-TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair.
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| |
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| Overall design |
8 ChIP-seq samples from in vritro cultured rat Schwann cells
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| |
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| Contributor(s) |
He X, Zhang L, Lu R |
| Citation(s) |
29431744 |
| Submission date |
Jan 04, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard Lu |
| Organization name |
Cincinnati Children's Hospital Medical Center
|
| Department |
CBDI
|
| Lab |
Lu Lab,T6.525
|
| Street address |
3333 Burnet Ave
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL14844 |
Illumina HiSeq 2000 (Rattus norvegicus) |
|
| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE93161 |
A Histone Deacetylase 3-Dependent Pathway Delimits Peripheral Myelin Growth and Functional Regeneration |
|
| Relations |
| BioProject |
PRJNA360160 |
| SRA |
SRP096082 |
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