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| Status |
Public on Apr 24, 2019 |
| Title |
Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and preventing aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domain. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1g Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathological and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA-independent role for DGCR8 in maintaining heterochromatin organization and preventing senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.
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| Overall design |
H3K9me3 ChIP-seq profiles of DR8dex2 hMSCs transduced with Luc, DR8-WT, or DR8-mtDRBD
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| |
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| Contributor(s) |
Liu G |
| Citation(s) |
31350386 |
| Submission date |
Apr 23, 2019 |
| Last update date |
Aug 06, 2019 |
| Contact name |
Zunpeng Liu |
| E-mail(s) |
zunpengliu@163.com
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| Phone |
+86 15510715055
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| Organization name |
State Key Laboratory of Stem Cell and Reproductive Biology
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| Department |
Institute of Zoology, Chinese Academy of Sciences
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| Lab |
Jing Qu
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| Street address |
Beichen West Road
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| City |
Beijing |
| ZIP/Postal code |
100101 |
| Country |
China |
| |
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| Platforms (1) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA534277 |
| SRA |
SRP193489 |
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