Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TOP2 synergizes with BAF chromatin remodeling for resolution of facultative heterochromatin

ABSTRACT: Resolution and formation of facultative heterochromatin is essential to development, reprogramming, and oncogenesis. The mechanisms underlying these changes are poorly understood due to difficulty with interrogating heterochromatin dynamics and structure in vivo. BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes are known to promote chromatin accessibility. As the function of topoisomerase IIa (TOP2A) is largely dependent on BAF complexes in embryonic stem (ES) cells, we tested whether TOP2 was involved in BAF-mediated resolution of heterochromatin by performing ATAC-seq on ES cells treated with the TOP2 inhibitor ICRF-193, Brg1 (the primary ATPase subunit of esBAF complexes) conditional knockout cells, and Baf53a (a non-catalytic subunit dispensable for in vitro remodeling) conditional knockout cells. We found that TOP2 synergizes with BAF complexes genome-wide to resolve facultative heterochromatin to accessible chromatin at a large number of regulatory elements.

ORGANISM(S): Mus musculus

PROVIDER: GSE94039 | GEO | 2017/03/01

SECONDARY ACCESSION(S): PRJNA368641

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The study of dpf2 in mouse ES cells

Project description:Brg-or Brm-associated factor (BAF) complexes, is a 12 subunit complex which contains an ATPase subunit, Brg or Brm, that uses energy derived from ATP hydrolysis to disrupt histone:DNA contacts to catalyze transcriptional events such as promoting gene expression or repression. Genetic studies in mice demonstrated that BAF complexes are essential for early embryonic development and pluripotency. ES cells express distinctive compleses, termed esBAF complexes by the presence of BAF155, Brg, BAF60a. Purification of Brg and Brm-associated proteins reveals a new family of four stoichiometric subunits of mSWI/SNF or BAF complexes which was termed BAF45a, b, c, and d. The progenitors to both neurons and glia are maintained in a proliferative state by a specified SWI/SNF-like npBAF complex that contains both BAF45a and BAF53a. The transition from proliferative to neurogenic divisions requires the exchange of these subunites for the homologous BAF45b or BAF45c and BAF53b proteins. The function of BAF45d remwains unclear so far.At present, we found that the knockout of dpf2 in ES cells impared the differention of ES cells. We will identify the target genes of dpf2 by Chip-seq so that we could study how dpf2 affect the differentiation of ES cells into germ layers.Protocol: DNA was prepared from ES cells by standard ChIP method. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/

2013-09-30 | E-ERAD-24 | biostudies-arrayexpress

esBAF chromatin remodeling complexes promote spacing of nucleosomes flanking pluripotency factor binding sites

Project description:We showed that topoisomerase II synergizes with BAF (mSWI/SNF) ATP-dependent chromatin remodeling complexes genome-wide to resolve facultative heterochromatin to accessible chromatin. To study the consequences of this on transcription factors, we performed MNase-seq on light digest of native chromatin in Brg1 conditional knockout embryonic stem (ES) cells. We found that spacing of nucleosomes flanking pluripotency factor binding sites specifically partially collapsed upon Brg1 deletion, indicating that pluripotency factor binding is likely lost.

2017-03-01 | GSE94040 | GEO

Altered BAF53A (ACTL6A) Stoichiometry Drives Human Squamous Cell Carcinoma [CnR]

Project description:To determine whether the chromatin accessibility for YAP/TEADs in squamous cell carcinoma cells is directly regulated by BAF53A within BAF complexes, we performed CUT&RUN to profile the distribution of YAP, TEAD1, and BAF155 (a DNA binding subunit of BAF complexes) across the genome.

2021-10-29 | GSE156787 | GEO

TOP2 synergizes with BAF chromatin remodeling for both resolutions and formation of facultative heterochromatin

Project description:TOP2 synergizes with BAF chromatin remodeling for both resolutions and formation of facultative heterochromatin

| PRJNA368632 | ENA

BAF subunit switching regulates chromatin accessibility to control cell cycle exit in the developing mammalian cortex [RNA-seq]

Project description:mSWI/SNF or BAF chromatin regulatory complexes are dosage-sensitive regulators of human neural development frequently mutated in autism and intellectual disability. Cell cycle exit and differentiation of neural stem/progenitor cells is accompanied by BAF subunit switching to generate neuron-specific nBAF complexes. We manipulated the timing of BAF subunit exchange in vivo and found that early loss of the npBAF subunit BAF53a stalls cell cycle exit to disrupt neurogenesis. Loss of BAF53a results in decreased chromatin accessibility at specific neural transcription factor binding sites, including the pioneer factors Sox2 and Ascl1, due to Polycomb accumulation. This results in repression of cell cycle genes, thereby blocking cell cycle progression and differentiation. Cell cycle block upon Baf53a deletion could be rescued by premature expression of the nBAF subunit BAF53b but not by other major drivers of proliferation or differentiation. Wnt, EGF, FGF, Sox2, myc or Pax6 all fail to maintain proliferation in the absence of BAF53a, highlighting a novel mechanism underlying neural progenitor cell cycle exit in the continued presence of extrinsic proliferative cues.

2021-01-18 | GSE164990 | GEO

BAF subunit switching regulates chromatin accessibility to control cell cycle exit in the developing mammalian cortex [ATAC-seq]

2021-01-18 | GSE164989 | GEO

Baf53a is involved in survival of mouse ES cells, which can be compensated by Baf53b.

Project description:The human Baf (Brg1/Brm associated factor) complex, also known as the mammalian SWI/SNF chromatin-remodeling complex, is involved in a variety of cellular processes. The pluripotency and self-renewal abilities are major characteristics of embryonic stem (ES) cells and are regulated by the ES cell-specific BAF (esBAF) complex. Baf53a is one of the subunits of the esBAF complex. Here, we found that growth of Baf53a-deficient ES cells was repressed, and expression of p53, p21, and cleaved Caspase 3 was increased. Interestingly, Baf53b, a homologue of Baf53a, rescued cell death of Baf53a-deficient ES cells. Baf53a-deficient ES cells overexpressing exogenous Baf53a or Baf53b remained in the undifferentiated state and proliferated. In summary, our findings suggest that Baf53a is involved in the survival of ES cells, and that Baf53b is able to compensate for this functional aspect of Baf53a.

2017-11-16 | GSE103694 | GEO

Mus musculus

Project description:TOP2 synergizes with BAF chromatin remodeling for resolution of facultative heterochromatin

| PRJNA368641 | ENA

mSWI/SNF (BAF) Complexes Facilitate Decatentation of DNA by Topoisomerase IIa

Project description:Recent exon sequencing studies of human tumors have revealed that subunits of mSWI/SNF or BAF complexes are mutated in more than 20% of human malignancies, yet the mechanisms involved in tumor suppression is unclear. BAF chromatin remodeling complexes are polymorphic assemblies that use energy provided by ATP hydrolysis to regulate transcription through the control of chromatin structure and the placement of Polycomb (PcG) across the genome. Several proteins dedicated to this large multi-subunit complex, including SMARCA4 (BRG1) and BAF250A (ARID1A), are mutated at frequencies similar to that of many recognized tumor suppressors. In particular, the core ATPase BRG1 is mutated in 5-10% of childhood medulloblastoma (MB) and greater than 15% of Burkitt's Lymphoma (BL). Here we find a novel function of BAF complexes in decatenating newly replicated sister chromatids, which is necessary for proper chromosome segregation during mitosis. We find that deletion of Brg1, as well as the expression of Brg1 point mutants identified in human tumors leads to anaphase bridge formation (sister chromatids linked by catenated strands of DNA), and a G2/M phase block characteristic of the decatenation checkpoint. Endogenous BAF complexes directly interact with endogenous TopoIIα through BAF250a and are required for TopoIIα binding to about 12,000 sites over the genome. Our results indicate that TopoIIα’s chromatin binding is dependent on the ATPase activity of Brg1, which is compromised in oncogenic Brg1 mutants. These studies indicate that the ability of TopoIIα to prevent DNA entanglement at mitosis requires BAF complexes and suggest that this activity contributes to the role of BAF subunits as tumor suppressors. Examination of sites of TopoIIa activity in WT and Brg1-/- ES cells as defined by TopoIIa-DNA covalent adducts formed in the presence of etoposide

2013-03-30 | E-GEOD-45625 | biostudies-arrayexpress

Top1 and Top2-mediated replication fork integrity

Project description:DNA topoisomerases solve topological problems during chromosome metabolism. We investigated where and when Top1 and Top2 are recruited on replicating chromosomes and how their inactivation affects fork integrity and DNA damage checkpoint activation. We show that, in the context of replicating chromatin, Top1 and Top2 act within a 600 bp region spanning the moving forks. Top2 exhibits additional S-phase clusters at specific intergenic loci, mostly containing promoters. TOP1 ablation does not affect fork progression and stability and does not cause activation of the Rad53 checkpoint kinase. top2 mutants accumulate sister chromatid junctions in S phase without affecting fork progression and activate Rad53 at the M/G1 transition. top1 top2 double mutants exhibit fork block and processing, and phosphorylation of Rad53 and γH2A in S phase. The exonuclease Exo1 influences fork processing and DNA damage checkpoint activation in top1 top2 mutants. Our data are consistent with a coordinated action of Top1 and Top2 in counteracting the accumulation of torsional stress and sister chromatid entanglement at replication forks, thus preventing the diffusion of topological changes along large chromosomal regions. A failure in resolving fork-related topological constrains during S phase may therefore result in abnormal chromosome transitions, DNA damage checkpoint activation and chromosome breakage during segregation. Keywords: ChIP-chip analysis

2007-08-01 | GSE8305 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data