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| Status |
Public on May 01, 2024 |
| Title |
The chromatin remodeling factor Arid1a cooperates with Jun/Fos to promote osteoclastogenesis by epigenetically upregulating Siglec15 expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Osteoporosis is characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-related bone formation, particularly increased osteoclastogenesis. However, the mechanisms by which epigenetic factors regulate osteoclast precursor differentiation during osteoclastogenesis remain poorly understood. Here, we show that the specific knockout of the chromatin remodeling factor Arid1a in bone marrow?derived macrophages (BMDMs) results in increased bone mass. The loss of Arid1a in BMDM inhibits cell?cell fusion and maturation of osteoclast precursors, thereby suppressing osteoclast differentiation. Mechanistically, Arid1a increases the chromatin access in the gene promoter region of sialic acid?binding Ig-like lectin 15 (Siglec15) by transcription factor Jun/Fos, which results in the upregulation of Siglec15 and promotion of osteoclast differentiation. However, the loss of Arid1a reprograms the chromatin structure to restrict Siglec15 expression in osteoclast precursors, thereby inhibiting BMDM differentiation into mature osteoclasts. Deleting Arid1a after ovariectomy (a model for postmenopausal bone loss) alleviated bone loss and maintained bone mass. In summary, epigenetic reprogramming mediated by Arid1a loss suppresses osteoclast differentiation and may serve as a promising therapeutic strategy for treating bone loss diseases.
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| Overall design |
Comparison of gene expression profiles and chromatin accessibility during osteoblast differentiation after Arid1a knockout. *Submitters did not provide the processed data for ATAC-Seq and CUT&Tag.
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| Contributor(s) |
Zhang Y, Sun H, Huang F, Shen L, Ye Z |
| Citation(s) |
38477755 |
| |
| Submission date |
May 08, 2023 |
| Last update date |
May 07, 2024 |
| Contact name |
Zhaoming Ye |
| E-mail(s) |
[email protected]
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| Organization name |
The Second Affiliated Hospital, Zhejiang University School of Medicine
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| Street address |
88 jiefang road
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| City |
hangzhou |
| ZIP/Postal code |
310031 |
| Country |
China |
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| Platforms (2) |
| GPL21273 |
HiSeq X Ten (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (37)
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| Relations |
| BioProject |
PRJNA970261 |
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