Mus musculus strain:C57BL/6J
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340036 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4064534.fastq.gz | Fastqsanger.gz | |||
| SRR4064535.fastq.gz | Fastqsanger.gz | |||
| SRR5189254.fastq.gz | Fastqsanger.gz | |||
| SRR5189254_1.fastq.gz | Fastqsanger.gz | |||
| SRR5189254_2.fastq.gz | Fastqsanger.gz |
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Project description:Differentiation of haematopoietic stem cells followsa hierarchical program of transcription-factor regulated events. Early myeloid cell differentiation is dependent on PU.1 and CEBPA (CCAAT/enhancer binding protein alpha), late myeloid differentiation is orchestrated by CEBPE (CCAAT/enhancer binding protein epsilon). The influence of SWI/SNF (SWItch/Sucrose Non-Fermentable) chromatin remodelling factors as novel master regulators of haematopoietic differentiation is only beginning to be explored. Here, we identified three homozygous loss-of-function mutations in SMARCD2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily d, member 2), a member of the SWI/SNF complex, in three unrelated pedigrees. We find that SMARCD2-deficient hematopoiesis results in dysfunctional neutrophil granulocytes, characterized by specific granule deficiency, myelodysplasia, and an excess of blast cells. We can show that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells in mice and zebra fish. In vitro SMARCD2 interacts with the transcription factor CEBPE. Furthermore, we find that SMARCD2 controls expression of neutrophil proteins stored in specific granules and leads to transcriptional and chromatin changes in AML cells. Hence, we identify SMARCD2 as a key factor controlling myelopoiesis and as a potential tumour suppressor in leukemia.
2017-01-18 | GSE84703 | GEO
Project description:Switch defective/sucrose non-fermentable (SWI/SNF) complexes are evolutionarily conserved multi-subunit machines that play vital roles in chromatin architecture regulation for modulating gene expression via sliding or ejection of nucleosomes in eukaryotes. In plants, perturbations of SWI/SNF subunits often result in severe developmental disorders. However, the subunit composition, pathways of assembly, and genomic targeting of the plant SWI/SNF complexes remain undefined. Here, we reveal that Arabidopsis SWI/SNF complexes exist in three distinct final form assemblies: BRM-associated SWI/SNF complexes (BAS), SYD-associated SWI/SNF complexes (SAS) and MINU-associated SWI/SNF complexes (MAS). We show that BAS complexes are equivalent to human ncBAF, whereas SAS and MAS complexes evolve in multiple subunits unique to plants, suggesting a plant-specific functional evolution of SWI/SNF complexes. We further demonstrate overlapping and specific genomic targeting of the three plant SWI/SNF complexes on chromatin and reveal that SAS complexes are necessary for the correct genomic localization of the BAS complexes. Finally, by focusing on the SAS and BAS complexes, we establish a requirement for both the core module subunit and the ATPase in the assembly of the plant SWI/SNF complexes. Together, our work highlights the divergence of SWI/SNF chromatin remodelers during the eukaryote evolution and provides a comprehensive landscape for understanding the plant SWI/SNF complexes organization, assembly, genomic targeting, and function.
2023-04-24 | GSE218841 | GEO
Project description:Bromodomain-containing protein 9 (BRD9) was recently identified to be associated with the chromatin remodeling SWI/SNF(BAF) complex, yet its function within the complex has remained unclear. Here, using genome-scale CRISPR-Cas9 screens, we found that BRD9 constitutes a specific vulnerability in highly malignant pediatric rhabdoid tumors, which are driven by inactivating mutations of SMARCB1 subunit of SWI/SNF complexes. Surprisingly, we found that BRD9 does not belong to the previously identified BAF or PBAF complexes, but instead is found exclusively in a novel of SWI/SNF sub-complex. We show that BRD9-containing complexes lack SMARCB1, which had previously been considered a core subunit present in all SWI/SNF variants. We recently demonstrated that both SMARCB1-containing and ARID1A-containing SWI/SNF complexes preferentially function at enhancers, but here we show that BRD9-containing complexes are located at active promoters as well as enhancers. We show that loss of SMARCB1, as observed in rhabdoid tumors, results in increased BRD9 interaction with SWI/SNF core subunit SMARCC1, consistent with competition between SMARCB1 and BRD9 in the formation of SWI/SNF complexes. Underlying the dependency, we demonstrate that BRD9, via its DUF3512 domain, is essential for maintaining the integrity of its sub-complex, which predominates in the absence of SMARCB1. Taken together, our results reveal a BRD9-containing SWI/SNF subcomplex which is required for the survival of SMARCB1-mutant rhabdoid tumors.
2019-03-14 | GSE125775 | GEO
Project description:Bromodomain-containing protein 9 (BRD9) was recently identified to be associated with the chromatin remodeling SWI/SNF(BAF) complex, yet its function within the complex has remained unclear. Here, using genome-scale CRISPR-Cas9 screens, we found that BRD9 constitutes a specific vulnerability in highly malignant pediatric rhabdoid tumors, which are driven by inactivating mutations of SMARCB1 subunit of SWI/SNF complexes. Surprisingly, we found that BRD9 does not belong to the previously identified BAF or PBAF complexes, but instead is found exclusively in a novel of SWI/SNF sub-complex. We show that BRD9-containing complexes lack SMARCB1, which had previously been considered a core subunit present in all SWI/SNF variants. We recently demonstrated that both SMARCB1-containing and ARID1A-containing SWI/SNF complexes preferentially function at enhancers, but here we show that BRD9-containing complexes are located at active promoters as well as enhancers. We show that loss of SMARCB1, as observed in rhabdoid tumors, results in increased BRD9 interaction with SWI/SNF core subunit SMARCC1, consistent with competition between SMARCB1 and BRD9 in the formation of SWI/SNF complexes. Underlying the dependency, we demonstrate that BRD9, via its DUF3512 domain, is essential for maintaining the integrity of its sub-complex, which predominates in the absence of SMARCB1. Taken together, our results reveal a BRD9-containing SWI/SNF subcomplex which is required for the survival of SMARCB1-mutant rhabdoid tumors.
2019-03-14 | GSE120233 | GEO
Project description:Bromodomain-containing protein 9 (BRD9) was recently identified to be associated with the chromatin remodeling SWI/SNF(BAF) complex, yet its function within the complex has remained unclear. Here, using genome-scale CRISPR-Cas9 screens, we found that BRD9 constitutes a specific vulnerability in highly malignant pediatric rhabdoid tumors, which are driven by inactivating mutations of SMARCB1 subunit of SWI/SNF complexes. Surprisingly, we found that BRD9 does not belong to the previously identified BAF or PBAF complexes, but instead is found exclusively in a novel of SWI/SNF sub-complex. We show that BRD9-containing complexes lack SMARCB1, which had previously been considered a core subunit present in all SWI/SNF variants. We recently demonstrated that both SMARCB1-containing and ARID1A-containing SWI/SNF complexes preferentially function at enhancers, but here we show that BRD9-containing complexes are located at active promoters as well as enhancers. We show that loss of SMARCB1, as observed in rhabdoid tumors, results in increased BRD9 interaction with SWI/SNF core subunit SMARCC1, consistent with competition between SMARCB1 and BRD9 in the formation of SWI/SNF complexes. Underlying the dependency, we demonstrate that BRD9, via its DUF3512 domain, is essential for maintaining the integrity of its sub-complex, which predominates in the absence of SMARCB1. Taken together, our results reveal a BRD9-containing SWI/SNF subcomplex which is required for the survival of SMARCB1-mutant rhabdoid tumors.
2019-03-14 | GSE120234 | GEO
Project description:SWI/SNF is a family of multi-subunit chromatin remodelling complexes comprised of BAF, PBAF and ncBAF. These complexes have diverse roles in cellular processes including transcription, replication, and repair, and play an important role in maintaining genome stability, with over 20% of all cancers having deleterious mutations in a SWI/SNF subunit. We modelled SWI/SNF dysfunction in the widely used cell line, RPE1, by engineering loss of function mutations in both shared and complex-specific subunits, as well as using small molecule treatment to acutely degrade or inhibit SWI/SNF. To analyse the functional consequences of this dysfunction, we performed transcriptomic analysis and compared this with whole cell and chromatin-bound proteomes. Strikingly, SWI/SNF-dependent changes in the transcriptome correlated poorly with changes at the protein level, while changes at the whole protein level correlated well with changes in proteins bound to chromatin. Comparative analyses of protein dynamics revealed that both acute and chronic SWI/SNF loss led to decreased association of cohesin and CTCF with chromatin, and that SWI/SNF remodelling activity was required for the maintenance of cohesin on chromatin. Notably, SWI/SNF loss also led to cohesin and CTCF localising to novel regions in the genome, and the patterns of mislocalisation showed subunit-specific patterns, suggesting that different SWI/SNF complexes have non-redundant impacts on cohesin localisation. Importantly, we find that the relationship between SWI/SNF and cohesin is functionally important, and cells lacking SWI/SNF show significant sensitivity to perturbation of cohesin. Our results highlight SWI/SNF complexes as critical regulators of cohesin dynamics and uncover a vulnerability that has therapeutic potential for cancers driven by SWI/SNF dysregulation.
2026-02-20 | PXD065273 | Pride
Project description:Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of these complexes, physiological roles for this domain remain undefined. We screened an N-ethyl-N-nitrosurea (ENU) mutagenized library for ARID domain point mutations and generated an Arid1a/Baf250a hypomorphic allele. The mutant ARID1a (V1068G) protein is stably expressed at wild-type levels, and it is capable of assembling into a SWI/SNF complex with in vitro mononucleosome disruption activity. However, its capacity to bind DNA is lost. Consistent with defective DNA binding, mutant protein occupancy at known SWI/SNF target genes is decreased. Loss of DNA binding is associated with concurrent changes in SWI/SNF target gene expression. Mutant embryos manifest heart defects, fail to establish proper yolk sac vasculature, and exhibit hemorrhaging. As a result of these phenotypes, mutant embryos fail to establish proper circulation, culminating in ischemic arrest in utero between days 9.5 and 11.5. These data support a role for ARID1a-containing, BAF-A complexes in heart and extraembryonic vascular development, and indicate the ARID domain of ARID1a is essential in this regard. Hence, intrinsic ARID subunit-DNA interactions are required for normal SWI/SNF function in vivo. Four-condition experiment, wild-type vs Baf250a/Arid1a^V1068G/V1068G yolk sacs isolated at E8.5 and E9.5. Biological replicates: 3 per condition.
2012-01-15 | E-GEOD-32116 | biostudies-arrayexpress
Project description:The composition of chromatin remodeling complexes dictates how these enzymes control transcriptional programs and cellular identity. Here, we investigate the composition of SWI/SNF complexes in embryonic stem cells (ESCs). In contrast to differentiated cells, ESCs have a biased incorporation of certain paralogous SWI/SNF subunits, with low levels of Brm, BAF170 and ARID1B. Upon differentiation, the expression of these subunits increases, resulting in a higher diversity of compositionally distinct SWI/SNF enzymes. We also identify Brd7 as a novel component of the PBAF complex in both ESCs and differentiated cells. Using shRNA-mediated depletion of Brg1, we show that SWI/SNF can function as both a repressor and an activator in pluripotent cells, regulating expression of developmental modifiers and signaling components such as Nodal, ADAMTS1, Bmi-1, CRABP1 and TRH. Knock-down studies of PBAF-specific Brd7 and of a signature subunit within the BAF complex, ARID1A, show that these two sub-complexes affect SWI/SNF target genes differentially, in some cases even antagonistically. This may be due to their different biochemical properties. Finally, we examine the role of SWI/SNF in regulating its target genes during differentiation. We find that SWI/SNF affects recruitment of components of the pre-initiation complex in a promoter-specific manner, to modulate transcription positively or negatively. Taken together, our results provide insight into the function of compositionally diverse SWI/SNF enzymes that underlie their inherent gene-specific mode of action. R1 ESCs were infected in duplicates with shRNA targeting Brg1 or GLUT4 (as a control). Knockdown of Brg1 mRNA affected Brg1 protein levels efficiently. RNA was isolated 67 hours post-infection and analyzed using microarrays.
2010-03-04 | E-GEOD-7791 | biostudies-arrayexpress
Project description:SWI/SNF chromatin remodeling complexes control gene expression by regulating chromatin structure. However, the full subunit composition of SWI/SNF complexes in plants remains unclear. Here we show that BRAHMA Interacting Protein 1 (BRIP1) and BRIP2 in Arabidopsis thaliana are core subunits of plant SWI/SNF complexes. BRIP1 and 2 are two homolog proteins. brip1 brip2 double mutants exhibit developmental phenotypes and a transcriptome strikingly similar to those of BRAHMA (BRM) mutants. Genetic interaction tests indicated that BRIP1 and 2 act together with BRM to regulate gene expression. Furthermore, BRIP1 and 2 physically interact with BRM-containing SWI/SNF complexes, and extensively co-localize with BRM at endogenous genes. Loss-of-brip1brip2 results in decreased BRM occupancy at almost all BRM target genes and substantially reduced subunits incorporation into the BRM-containing SWI/SNF complexes. Together, our work identifies new core subunits of BRM-containing SWI/SNF complexes in plants, and uncovers the essential role of these subunits in regulating the integrity (assembly) of SWI/SNF complexes in plants.
2020-06-21 | GSE142621 | GEO
Project description:The SWI/SNF family of chromatin remodeling complexes is evolutionarily conserved and present in yeast, animals and plants. While the biological functions of plant SWI/SNF complexes have been studied in detail, their composition is still elusive. To clarify this picture we used protein extracts from Arabidopsis plants in vegetative phase of growth to perform a series of immunoprecipitation followed by mass spectrometry experiments, using GFP-tagged BRM ATPase as a bait. The analysis of MS data showed that the dominant form of SWI/SNF complex present in these extracts has a specific subunit composition including ARP4 and 7, SWI3C, SWP73B and BRIP2, as well as three bromodomain containing subunits, BRD1, 2 and 13. This subunit composition and the lack of the core SWI/SNF subunit BSH (SNF5/INI1) both strongly resemble the characteristics of the specific subclass of mammalian SWI/SNF complexes referred to as non-canonical BAFs, indicating that homologues of these complexes also exist in plants. We next found that depletion of the all three BRDs severely affected the assembly of this form of BRM-associated SWI/SNF complex. However, while BRD1 and BRD2 were found sufficient to allow complex formation, BRD13 was only required under BRD1/2 deficiency. The analyses of IP/MS results using BRM-GFP in different brd mutant backgrounds as well as BRD1-GFP indicate that SWI/SNF assemblies containing only one BRD isoform, BRD1 or BRD2, do exist. Furthermore, our data indicate that BRD1/2 may be necessary for the incorporation of BRIP2 subunit into the complex. Together, our results shed new light on the structural and functional diversification of SWI/SNF complexes in Arabidopsis.
2023-04-03 | PXD030928 | Pride