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| Status |
Public on Oct 31, 2023 |
| Title |
BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ChIP-Seq II] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Chromatin remodeling caused by SWI/SNF (BAF) complexes is essential for regulating cell fates. Of these, BRD9, an essential component of the non-canonical BAF (ncBAF) complex, is post-transcriptionally decayed in multiple types of cancer, especially in myelodysplastic syndrome (MDS). However, how BRD9 loss or ncBAF disruption alters the HSCs' integrity remains unknown. Here, we identify that Brd9 loss enhances chromatin accessibility, promoting myeloid-lineage skewing at the expense of B cell development in vivo, followed by MDS development. Brd9 significantly colocalizes with Ctcf, whose peaks are stoichiometrically enhanced by Brd9 loss, leading to increased chromatin loops with the larger chromatin domains intact. These Ctcf-associated chromatin loops newly occur in myeloid-related genes. These data uncover the unrecognized roles of BRD9/ncBAF in the cell fate specification of HSCs via fine-tuning chromatin loops and shed light on the mechanism of ncBAF-disrupted cancer.
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| Overall design |
2.0 x 10E6 total BM cells of Mx1-Cre control, Mx1-Cre Brd9fl/fl mice transplanted via tail vein injection into lethally irradiated (two times 450 cGy) CD45.1+ recipient mice. Four weeks after BMT, the recipient mice received 20 mg/kg pIpC injection every other day for a total of 3 doses. Five months after pIpC injection, the recipient mice were sacrificed for sample preparation.
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| Contributor(s) |
Nomura M, Kondo S, Xiao M, Inoue D |
| Citation(s) |
38102116 |
| |
| Submission date |
May 18, 2022 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Masaki Nomura |
| E-mail(s) |
masaki.nomura.fbri@gmail.com
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| Organization name |
Foundation for Biomedical Research and Innovation at Kobe
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| Street address |
6-3-7 Minatojima Minamimachi, Chuo Ward
|
| City |
Kobe |
| State/province |
Hyogo |
| ZIP/Postal code |
650-0047 |
| Country |
Japan |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE203322 |
BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state |
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| Relations |
| BioProject |
PRJNA839420 |
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