Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SWI/SNF is positively auto-regulated by an AT-hook in the catalytic subunit

ABSTRACT: The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome; controlling pluripotency, cell fate determination and differentiation. There is a sparsity of information on the autoregulation of SWI/SNF, the domains involved and their mode of action. We find a DNA or RNA binding module conserved from yeast to humans located in the C-terminus of the catalytic subunit of SWI/SNF called the AT-hook that positively regulates the chromatin remodeling activity of yeast and mouse SWI/SNF. The AT-hook in yeast SWI/SNF interacts with the SnAC and ATPase domains, which after binding to nucleosome switches to contacting the N-terminus of histone H3. Deletion of the AT-hooks in yeast SWI/SNF and mouse esBAF complexes reduces the remodeling activity of SWI/SNF without affecting complex integrity or its recruitment to nucleosomes. In addition, deletion of the AT-hook impairs the ATPase and nucleosome mobilizing activities of yeast SWI/SNF without disrupting the interactions of the ATPase domain with nucleosomal DNA. The AT-hook is also important in vivo for SWI/SNF-dependent response to amino acid starvation in yeast and for cell lineage priming in mouse embryonic stem cells. In summary, the AT-hook is shown to be an evolutionarily conserved autoregulatory domain of SWI/SNF that positively regulates SWI/SNF both in vitro and in vivo.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Jie Luo

LAB HEAD: Jeff Ranish

PROVIDER: PXD040664 | Pride | 2023-06-15

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	JL021919_030919_ySwiSnf_NCP_100B.mzXML	Mzxml
	JL021919_030919_ySwiSnf_NCP_1ug.mzXML	Mzxml
	JL021919_030919_ySwiSnf_NCP_30B.mzXML	Mzxml
	JL021919_030919_ySwiSnf_NCP_50B.mzXML	Mzxml
	JL021919_030919_ySwiSnf_NCP_70B.mzXML	Mzxml

Items per page:

1 - 5 of 10

Similar Datasets

Yeast SWI/SNF complex - Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex

Project description:This project uses crosslinked based mass spectrometry (CXMS) to study the architecture of yeast SWI/SNF complex.

2018-06-14 | PXD005948 | Pride

Analysis of proteins that bind promoter of the PDR5 multidrug transporter gene in Saccharomyces cerevisiae using minichromosome isolation and LC-MS/MS

Project description:The Pleiotropic Drug Resistance (PDR) network is central to the drug response in fungi, and its overactivation is associated with drug resistance. However, gene regulation of the PDR network is not well understood. Here, we established a method to identify proteins that bind promoter of the PDR5 multidrug transporter gene in Saccharomyces cerevisiae using minichromosome isolation and SILAC-based quantitative proteomics, and identified the SWI/SNF chromatin remodelling complex as a PDR5 promoter-binding complex. We also purified the SWI/SNF complex from S. cerevisiae by immunoprecipitating Flag-tagged Snf6, a subunit of SWI/SNF, and identified the subunits of SWI/SNF and its binding proteins by LC-MS/MS.

2022-02-22 | PXD028798 | Pride

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming [ChIP-seq]

Project description:The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (KM). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. The catalytic subunit’s AT-hook is required in vivo for SWI/SNF remodeling activity in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of stage-specific enhancers critical in cell lineage priming. Similarly, growth assays suggest the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity.

2023-06-01 | GSE207792 | GEO

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming [ATAC-seq]

2023-06-01 | GSE207785 | GEO

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming [PRO-seq]

2023-06-01 | GSE207781 | GEO

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming [MNase-seq]

2023-06-01 | GSE219115 | GEO

Role of Specialized Composition of SWI/SNF Complexes in Prostate Cancer Lineage Plasticity

Project description:Advanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance seen in 10% of these patients is through lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify SWI/SNF subunits that are deregulated in NEPC, demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease and that SMARCA4 depletion impairs prostate cancer cell growth. We also show that SWI/SNF complexes interact with different lineage-specific factors in prostate adenocarcinoma and in NEPC cells, and that induction of lineage plasticity through depletion of REST is accompanied by changes in SWI/SNF genome occupancy. These data suggest a specific role for mSWI/SNF complexes in therapy-related lineage plasticity, which may be relevant for other solid tumors.

2020-11-04 | PXD016861 | Pride

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

Drosophila BAF complex crosslinking (

Project description:Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are large, multisubunit molecular machines that play vital roles in regulating genomic architecture and are frequently disrupted in human cancer and developmental disorders. To date, the organization and pathway of assembly of these chromatin regulators remain unknown, presenting a major barrier to structural and functional determination. Here we elucidate the architecture and assembly pathway of three different classes of mammalian SWI/SNF complexes: canonical BAF, PBAF, and a newly defined complex, ncBAF, and define the requirement of each subunit for complex formation and stability. Using affinity purification of endogenous complexes from mammalian and Drosophila cells coupled with cross linking-mass spectrometry, we uncover three distinct and evolutionarily conserved modules, their organization, and the temporal incorporation of these modules into each complete mSWI/SNF complex class.

2018-10-18 | PXD010123 | Pride

Human pBAF complex (HA-BRD7, PHF10-HA pulldown)

2018-10-18 | PXD010122 | Pride