Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [bulk RNA-Seq I]

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE203316 | GEO | 2023/10/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [mouse_Brd9_ATAC-seq]

Project description: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.

2023-10-31 | GSE236329 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [scRNA-Seq]

2023-10-31 | GSE203321 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ChIP-Seq II]

2023-10-31 | GSE203320 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ATAC-Seq II]

2023-10-31 | GSE203318 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ChIP-Seq I]

2023-10-31 | GSE203317 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [ATAC-Seq I]

2023-10-31 | GSE203315 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [bulk RNA-Seq II]

2023-10-31 | GSE203319 | GEO

A non-canonical SWI/SNF complex underlies synthetic lethality in cancers driven by BAF complex perturbation

Project description:Mammalian SWI/SNF chromatin remodeling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF, and a newly characterized non-canonical complex, ncBAF. However, their complex-specific targeting on chromatin, functions and roles in disease remain largely unknown. Here, we comprehensively map complex assemblies on chromatin and find that ncBAF uniquely localizes to CTCF sites and promoters. We identified ncBAF subunits as major synthetic lethalities specific to human synovial sarcoma and malignant rhabdoid tumor, which share in common cBAF complex perturbation. Chemical and biological depletion of the BRD9 subunit of ncBAF rapidly attenuates SS and MRT cell proliferation. Notably, in cBAF-perturbed cancers, ncBAF complexes retain localization to CTCF sites and promoters, and maintain gene expression at retained mSWI/SNF sites to support cell proliferation in a manner distinct from fusion oncoprotein-mediated targeting. Taken together, these findings unmask the unique targeting and function of ncBAF complexes and present new cancer-specific therapeutic targets.

2018-11-06 | PXD011103 | Pride

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state [mouse_Brd9_H3K27Ac-ChIP-seq]

Project description:Switch/sucrose nonfermentable (SWI/SNF) complexes are ATP-dependent chromatin remodeler complexes that play critical roles in timely and appropriate gene regulation by modulating chromatin architecture and DNA accessibility. SWI/SNF complexes can be grouped into three subcomplexes of differing sizes, canonical BAF (cBAF), polybromo BAF (PBAF), and newly identified noncanonical BAF (ncBAF). The most recently characterized ncBAF lacks the core BAF subunits ARID, BAF47, and BAF57, but includes unique subunits GLTSCR1/1L and BRD9, one of the bromodomain-containing proteins.We recently demonstrated the novel mechanism for the ncBAF disruption caused by mutations in a spiceosomal protein, SF3B1, especially in 65–83% for myelodysplastic syndromes (MDS) with ring sideroblasts as well as in >20% of mucosal/uveal melanomas, suggesting that the disturbed ncBAF may have some roles in the malignant hematopoiesis.Mechanistically, SF3B1 mutant recognizes an aberrant, deep intronic branchpoint within BRD9 and thereby induces the inclusion of an aberrant exon and subsequently profound degradation of BRD9 mRNA by triggering nonsense-mediated RNA decay (NMD). However, compared to the roles of cBAF, the functions of BRD9/ncBAF in normal and malignant hematopoiesis in vivo have been totally uncharacterized.

2023-10-31 | GSE236330 | GEO

BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state

2023-10-31 | GSE236960 | GEO