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| Status |
Public on Jun 22, 2020 |
| Title |
CTCF-dependent chromatin architecture and SUZ12/PRC2 complex recruitment are required for peripheral myelination and repair |
| Organisms |
Mus musculus; Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chromatin organization is critical for cell growth, differentiation, and disease development, however, its functions in peripheral myelination and myelin repair remain elusive. Here we observed a global diminution of chromatin accessibility during Schwann cell differentiation and demonstrated that the chromatin organizer CCCTC-binding factor (CTCF) is critical for Schwann cell myelination and myelin regeneration after nerve injury. Inhibition of Ctcf or its deletion blocked Schwann cell differentiation at the pre-myelinating stage, whereas overexpression of CTCF promoted the myelination program. CTCF establishes the chromatin interaction loop between promoters and regulatory elements to promote expression of key pro-myelinogenic factors such as EGR2. In addition, CTCF interacts with SUZ12, a component of polycomb-repressive-complex 2, to repress expression of immature Schwann cell-associated regulators including HES1, RSPO2, and CALCA. Together, our findings reveal the dual role of CTCF-dependent chromatin organization in promoting myelinogenic programs and recruiting chromatin-repressive complexes to block differentiation inhibitors to control peripheral myelination and myelin repair.
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| Overall design |
RNA-seq: 2 Control and 2 Ctcf cKO mouse sciatic nerves; 3 siControl and 3 siCtcf rat Schwann cell cultures. ChIP-seq: 1 proliferating and 1 differentiating samples for CTCF ChIP-seq; 1 siControl and 1 siCtcf samples for H3K27ac ChIP-seq. ATAC-seq: 2 siControl and 2 siCtcf samples.
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| Contributor(s) |
Wang J, Wang J, Yang L, Weng Q, Lu QR |
| Citation(s) |
32807777 |
| Submission date |
Sep 27, 2019 |
| Last update date |
Aug 31, 2020 |
| Contact name |
Richard Lu |
| Organization name |
Cincinnati Children's Hospital Medical Center
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| Department |
CBDI
|
| Lab |
Lu Lab,T6.525
|
| Street address |
3333 Burnet Ave
|
| City |
Cincinnati |
| State/province |
OH |
| ZIP/Postal code |
45229 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL18694 |
Illumina HiSeq 2500 (Rattus norvegicus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA574954 |
| SRA |
SRP223709 |
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