Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MSDC for identification of Pol II post-initiation complex changes

ABSTRACT: Mass Spectrometry with DTME Crosslinking (MSDC) based on label-free mass spectrometry to assess changes in the post-initiation Pol II complex.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Sicong Zhang

LAB HEAD: Robert Roeder

PROVIDER: PXD052484 | Pride | 2024-07-04

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	MS195059LUM_Sicong_Roeder_DBET6_a.raw	Raw
	MS195059LUM_Sicong_Roeder_IgG_a.raw	Raw
	MS195059LUM_Sicong_Roeder_NVP2_a.raw	Raw
	MS195059LUM_Sicong_Roeder_control_a.raw	Raw
	MS195167QEHF_Sicong_Roeder_Control.raw	Raw

Items per page:

1 - 5 of 10

Similar Datasets

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-10-23 | E-GEOD-62614 | biostudies-arrayexpress

Genome-Wide Yan Chromatin Occupancy in Drosophila Embryos

Project description:The ETS transcriptional repressor Yan functions as part of a developmental switch that in response to receptor tyrosine kinase signaling, transitions from a high-Yan to a low-Yan state to direct specification of a variety of cell fates. To date very few direct target genes have been identified, nor is it clear how their expression is buffered against developmental noise to prevent inappropriate oscillations between states. Following investigation of its genome-wide chromatin occupancy profile, we noticed a striking signature at developmentally important genes whereby Yan associates with chromatin in regions of high-peak density that span multiple kilobases which partially relies upon SAM-domain mediated self-association. We speculate that the high-density Yan occupancy signature may reveal a novel mechanism that buffers the expression of critical developmental regulators against intrinsic and environmental noise. The supplementary bed file contains Yan binding regions. Yan ChIP from staged Drosophila embryos

2013-03-01 | E-GEOD-34038 | biostudies-arrayexpress

Targeting transcriptional dependencies in cancer using a covalent CDK7 inhibitor (expression)

Project description:Cyclin-dependent kinase 7 (CDK7) plays a critical role in the general regulation of RNA polymerase II-mediated transcription. However, the absence of selective CDK7 inhibitors has hindered the ability to investigate the consequences of acute and prolonged inhibition of CDK7 under normal and pathological conditions. Here we present the discovery and characterization of the first covalent CDK7 inhibitor, CDK7-IN-1, that has the unprecedented ability to target a unique cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7 amongst the 20 known CDKs. Cancer cell line profiling indicates that a subset of cancer cell lines, including T-cell acute lymphoblastic leukemia (T-ALL), exhibit 100-fold greater sensitivity to CDK7-IN-1 over other tumor and normal cell lines. Genome-wide expression analysis in Jurkat T-ALL indicates that CDK7-IN-1 disproportionally affects RUNX1 as well as other components of the TAL1 transcriptional network and its targets, downregulating key regulators of transcription and apoptosis critical for the T-ALL state. These oncogenes are encoded by short-lived mRNA transcripts, are associated with super-enhancers, and exhibit a strong dependency on continuous transcription for sustained expression. Therefore, pharmacological modulation of CDK7 kinase activity may define a method for the identification and treatment of tumor types exhibiting extreme dependencies on transcription for maintenance of the oncogenic state. Jurkat, MM1S, Loucy, and HeLa (WT and Dox-inducible CDK7 mutant) cells were treated with various drugs including a covalent inhibitor of CDK7 (CDK7-IN-1), a reversible inhibitor of CDK7 (CDK7-IN-1), Flavopiridol, Actinomycin D, and DMSO controls. Replicates are annotated.

2014-06-22 | E-GEOD-50624 | biostudies-arrayexpress

Targeting Transcriptional Addictions in Small Cell Lung Cancer with a Covalent CDK7 Inhibitor (Affymetrix)

Project description:Small cell lung cancer (SCLC) is an aggressive disease with high mortality. The identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library we observe that SCLC is sensitive to transcription-targeting drugs, and in particular to THZ1, a newly identified covalent inhibitor of cyclin-dependent kinase 7 (CDK7). We find that expression of super-enhancer associated transcription factor genes including MYC family proto-oncogenes and neuroendocrine lineage-specific factors are highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a novel treatment paradigm for targeted SCLC therapy. Microarray expression in small cell lung cancer lines treated with DMSO or THZ1

2014-10-23 | E-GEOD-62609 | biostudies-arrayexpress

Cellular interactome dynamics during heat stress

Project description:Quantitative in vivo cross-linking-mass spectrometry was used to identify significant time-dependent interactome changes that occur prior to large-scale proteome abundance remodeling in cells subjected to heat stress. Interactome changes were identified within minutes of applied heat stress, including changes in chaperone systems as expected due to altered functional demand. Global analysis of all interactome changes revealed the largest significant enrichment in the class of RNA binding proteins, providing new time-dependent conformational insight on complex relationships that exist between transcription, translation and cellular stress response mechanisms upstream of transcriptional reprogramming. Observed interactome dynamics of RNA binding proteins that are also HSP90 clients constitute mechanistic changes that increase HSP90 functional demand, evident from observed HSP90 interactome changes early in heat stress. However, these changes together with observed heat stress-induced ATP level reduction result in observed complex time-dependent HSP90 interactome dynamics, indicating HSP90 conformational bottleneck formation with increased stress duration.

2024-11-25 | PXD058191 | Pride

C9orf72 ubiquitin and interaction proteomics

Project description:C9orf72 binds SMCR8 to from a robust complex that regulates small GTPases, lysosomal integrity and autophagy. In contrast to this functional understanding, we know far less about assembly and turnover of the C9orf72-SMCR8 complex. Loss of either subunit causes the concurrent ablation of the respective partner. However, the molecular mechanism underlying this interdependence remains elusive.

2023-05-10 | PXD039887 | Pride

Detained introns are novel, widespread class of posttranscriptionally-spliced introns

Project description:Removal of introns by pre-mRNA splicing is a critical and in some cases rate-limiting step in mammalian gene expression. Deep sequencing of mouse embryonic stem cell RNA revealed many specific internal introns that are significantly more abundant than the other introns within poly(A) selected transcripts; we classify these as “detained” introns (DIs). We identified thousands of DIs flanking both constitutive and alternatively spliced exons in human and mouse cell lines. Drug inhibition of Clk SR-protein kinase activity triggered rapid splicing changes in a specific set of DIs, about half of which showed increased splicing and half increased intron detention, altering the transcript pool of over 300 genes. These data suggest a widespread mechanism by which a nuclear detained pool of mostly processed pre-mRNAs can be rapidly mobilized in response to stress or homeostatic autoregulation. v6.5 mouse embryonic stem cells were untreated, treated with the Clk kinase inhibitor KH-CB19, or treated with DMSO as a negative control. Untreated cells were harvested and a single replicate was sequenced using a custom, ligation-based, stranded library preparation protocol. Treated cells were harvested at time 0 and at 2 hours post-treatment, and poly(A)-selected RNA-seq libraries were made from biological duplicates for each treatment/time, barcoded, and sequenced by strand-specific, paired-end sequencing using the Illumina TruSeq kit.

2015-01-15 | E-GEOD-57231 | biostudies-arrayexpress

Covalent inhibition of Plasmodium falciparum Ubc13 impairs global protein synthesis

Project description:The ubiquitin-conjugating enzyme 13 (Ubc13) has an essential function and putative role in artemisinin activity against Plasmodium falciparum. Ubc13 conjugates lysine 63-linked ubiquitin (K63-Ub) to proteins, but the role of this modification in Plasmodium remains largely unknown. Herein, we characterize and deploy NSC697923 to interrogate PfUbc13 function. We demonstrate that NSC697923 covalently targets the PfUbc13 active site residue and exhibits nanomolar inhibitory potency. NSC697923 displays anti-Plasmodium activity against drug-sensitive and drug-resistant asexual strains, gametocytes, and liver stage parasites, and synergizes with the malaria drug dihydroartemisinin. NSC697923 specifically reduces K63-Ub levels in asexual blood stage parasites, and subsequent ubiquitin pull-down assays and proteomic analyses identified putative PfUbc13 substrates. We highlight 37 proteins that overlapped with two previous ubiquitin datasets and were enriched in translation, transcription, and proteasome processes. A cellular puromycin-incorporation study demonstrated reduction of P. falciparum nascent protein synthesis following NSC697923 exposure, supporting a role for PfUbc13 and K63-Ub in mediating parasite protein translation. These findings expand our knowledge of the PfUbc13-dependent processes in these pathogenic parasites and highlight this enzyme as a potential antimalarial drug target.

2025-04-29 | PXD059643 | Pride

Global analysis of p53-regulated transcription reveals its direct targets and unexpected regulatory mechanisms

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-15 | E-GEOD-53966 | biostudies-arrayexpress

Global analysis of p53-regulated transcription reveals its direct targets and unexpected regulatory mechanisms (microarray)

Project description:HCT116 microarray done 12 hours after treatment with DMSO (control) or Nutlin Total RNA from HCT116 cells was harvested with an RNeasy kit (Qiagen) and analyzed on Affymetrix HuGene 1.0 ST arrays following the manufacturer’s instructions. Microarray data were processed using Partek Genomics Suite 6.6. Anova was used to call differentially expressed genes for which any isoform showed a fold change > |+/-1.5| with FDR <0.05. There were 362 genes called as upregulated and 367 genes as downregulated.

2014-05-15 | E-GEOD-53965 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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