Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mitogen induced-nucleosomal response pathway and transcriptional programming in mammalian fibroblasts

ABSTRACT: Stimulation of the RAS-MAPK pathway activates mitogen- and stress-activated kinases (MSK) 1 and 2, which phosphorylate histone H3 at S10 (H3S10ph) or S28 (H3S28ph) (nucleosomal response) located at the regulatory regions of immediate-early genes, setting in motion a series of chromatin remodeling events that result in transcription initiation. To investigate immediate-early genes regulated by the MSK, we have completed transcriptome analyses (RNA Sequencing) of human normal fibroblast cells (CCD-1070Sk) stimulated with EGF or TPA ± H89, a potent MSK/PKA inhibitor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE183856 | GEO | 2021/09/13

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2

Project description:Pervasive phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora B/C plays an important role in mitosis; however, this mark has also been observed at specific genic promoters and enhancers in interphase, implicating mitosis-independent functions. Using the FUCCI cell cycle reporter, we found that 30% of the genome is persistently marked with H3S10ph in interphase mouse embryonic stem cells (ESCs). H3S10ph demarcates broad gene-rich euchromatic regions in G1 and shows remarkable correlation with domains of early DNA replication timing (RT). Consistent with mitosis-independent H3S10 kinase activity, this pattern was preserved in ESCs treated with hesperidin, a potent inhibitor of Aurora B/C. Disruption of H3S10ph by expression of non-phosphorylatable H3.3S10A results in ectopic spreading of H3K9me2 into adjacent H3S10ph-enriched euchromatic regions, mimicking the phenotype observed in Drosophila JIL-1 kinase mutants. Conversely, H3S10ph domains expand in interphase Glp-/- ESCs, revealing that H3S10ph expansion is restricted by H3K9me2. Strikingly, spreading of H3S10ph at RT transition regions (TTRs) is accompanied by aberrant strand-biased transcription initiation of genes and repetitive elements co-oriented with the replication fork, indicating that H3K9me2 plays a critical role in establishing repressive chromatin on the leading strand. Finally, we show that H3S10ph is also present in interphase murine embryonic fibroblasts (MEFs), but is restricted to intragenic regions of actively transcribing genes. Our study provides a detailed map of interphase H3S10ph in ESCs and MEFs, uncovering a previously unappreciated crosstalk between the opposing marks H3S10ph and H3K9me2, and a role for the latter in ensuring appropriate transcription at TTRs in ESCs.

2017-11-20 | GSE97947 | GEO

Genome-wide analysis of the effects of the novel mithramycin analogue DIG-MSK on human A2780 ovarian carcinoma cells

Project description:The effects of demycarosyl-3D-M-NM-2-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), a novel analogue of the antitumor antibiotic mithramycin A, on gene transcription were examined in human A2780 ovarian carcinoma cells. DIG-MSK down-regulated a different set of genes depending on the drug concentration. Moreover, several genes were significantly up-regulated. These results are rationalized in terms of DIG-MSK competition with Sp1 transcription factor for binding to consensus C/G-rich tracts encompassed in gene promoters. Human A2780 ovarian carcinoma cells were treated with either 8 nM or 80 nM DIG-MSK for 24 h, and RNA was extracted from treated cells as well as from untreated (control) cells.

2014-08-13 | E-GEOD-46926 | biostudies-arrayexpress

Genome-wide analysis of the effects of the novel mithramycin analogue DIG-MSK on human A2780 ovarian carcinoma cells

Project description:The effects of demycarosyl-3D-β-D-digitoxosyl-mithramycin SK (DIG-MSK; EC-8042), a novel analogue of the antitumor antibiotic mithramycin A, on gene transcription were examined in human A2780 ovarian carcinoma cells. DIG-MSK down-regulated a different set of genes depending on the drug concentration. Moreover, several genes were significantly up-regulated. These results are rationalized in terms of DIG-MSK competition with Sp1 transcription factor for binding to consensus C/G-rich tracts encompassed in gene promoters.

2014-08-13 | GSE46926 | GEO

Signaling to histone H3 for augmented transcription in the inflammatory response

Project description:The inflammatory response depends upon selective, rapid transcription initiation and high-level generation of gene products for defense against pathogens and environmental insult1,2. Kinase cascades are broadly employed for rapid transmission of extracellular information, thereby regulating the cell’s environmental response. These pathways play a prominent role in the inflammatory process. Several kinases directly phosphorylate histone proteins in chromatin, representing a mechanism for the rapid modification of chromatin with the potential to regulate selective transcription responses to environmental cues3-10. However, the molecular functions of specific histone phosphorylation events in transcription are poorly understood. Here, we demonstrate a direct effect of histone H3 phosphorylation at serine 28 (H3S28p) on transcription activation and describe a prominent role for H3S28p in the amplification of inflammatory gene transcription following stimulation of mouse macrophages with bacterial lipopolysaccharide (LPS). We identify MSK kinases as the non-redundant kinases that mediate the rapid, stimulation-dependent deposition of H3S28p on chromatin. Pharmacological approaches, including the use of a novel chemical agent, reveal that MSK inhibition abolishes stimulation-dependent accumulation of H3S28p at LPS-induced genes and reduces production of inflammatory gene products. Mechanistically, H3S28p directly increases transcriptional output by augmenting recruitment of the transcription co-activator and histone acetyltransferase (HAT) p300, and increasing its HAT activity. Our results reveal a delegated role for H3S28p in selective augmentation of transcription during the rapid cellular response to environmental cues.

2016-10-31 | GSE63792 | GEO

Histone H3 tail interactome in MPC11 murine myeloma cells

Project description:We have used peptide capture in conjunction with super-SILAC quantification to carry out an unbiased high-throughput analysis of the composition of protein complexes that bind to histone H3K9/S10 and H3K27/S28 methyl-phospho modifications. We compared binding profiles of nuclear proteins from MPC11 myeloma cells to peptides carrying the H3K9me3, H3K27me3, H3S10ph, H3S28ph and the double H3K9me3/S10ph and H3K27me3/S28ph modifications. The analysis was carried out using peptides corresponding to amino acids 1-20 and 18-38 and the unmodified peptides were also analysed to assess binding to the unmodified histone tail. In order to ensure that the proteins present in any of the "heavy" capture assay samples have corresponding peptides in the common "light" internal reference, we adapted the super-SILAC approach using a reference sample that was obtained by mixing the 8 pulldowns and the negative beads-only control. The method allows us to accurately quantify binding and directly compare levels of binding to peptides that carry a number of different methyl-phospho combinations. This makes it possible for use indeatiled bioinformatic analyses.

2016-05-04 | PXD001273 | Pride

Comparative proteomic analysis of kidney distal convoluted tubule and cortical collecting duct cells following long-term hormonal stimulation

Project description:The distal convoluted tubule (DCT) and the cortical collecting ducts (CCD) are portions of renal tubule that are partly responsible for maintaining the systemic concentrations of potassium, sodium, calcium and magnesium. Despite being structurally similar, DCT and CCD cells have different transport capabilities due to a variety of different membrane-associated transport proteins. However, DCT and CCD cells appear to be modulated via the same hormones. The objective of this study was assess the differential response of DCT and CCD cells to long-term exposure to the hormones vasopressin or angiotensin II, both of which modulate DCT and CCD cells differently. Mass spectrometry based quantitative proteomics was used to profile the differential proteome between DCT and CCD.

2017-12-15 | PXD005454 | Pride

Proteomic-based research strategy identified laminin subunit alpha 2 as a potential urinary-specific biomarker for the medullary sponge kidney disease

Project description:Medullary sponge kidney (MSK) disease, a rare kidney malformation featuring recurrent renal stones and nephrocalcinosis, continues to be diagnosed using expensive and time-consuming clinical/instrumental tests (mainly urography). Currently, no molecular diagnostic biomarkers are available. To identify such we employed a proteomic-based research strategy utilizing urine from 22 patients with MSK and 22 patients affected by idiopathic calcium nephrolithiasis (ICN) as controls. Notably, two patients with ICN presented cysts. In the discovery phase, the urine of 11 MSK and 10 controls, were randomly selected, processed, and analyzed by mass spectrometry. Subsequently, several statistical algorithms were undertaken to select the most discriminative proteins between the two study groups. ELISA, performed on the entire patients’ cohort, was used to validate the proteomic results. After an initial statistical analysis, 249 and 396 proteins were identified exclusive for ICN and MSK, respectively. A Volcano plot and ROC analysis, performed to restrict the number of MSK-associated proteins, indicated that 328 and 44 proteins, respectively, were specific for MSK. Interestingly, 119 proteins were found to differentiate patients with cysts (all patients with MSK and the two ICN with renal cysts) from ICN without cysts. Eventually, 16 proteins were found to be common to three statistical methods with laminin subunit alpha 2 (LAMA-2) reaching the higher rank by a Support Vector Machine, a binary classification/prediction scheme. ELISA for LAMA-2 validated proteomic results. Thus, using high-throughput technology, our study identified a candidate MSK biomarker possibly employable in future for the early diagnosis of this disease.

2021-05-24 | PXD025744 | Pride

H3S10ph cistromes after eccentric contractions of mouse skeletal muscles

Project description:Genome-wide H3S10ph marks from mouse gastrocnemius muscles after 50 eccentric contractions compared to contralateral unstimulated gastrocnemius muscles from the same mice.

2020-05-17 | GSE139661 | GEO

ChIP-Seq in MSK-PCa3 Prostate Cancer Organoids of FOSL1, TAZ, TEAD1, YAP

Project description:Genome-wide mapping of FOSL1, YAP, TAZ and TEAD1 binding sites in MSK-PCa3 cells

2022-02-17 | GSE196732 | GEO

Transcriptomic profiles in dental pulp cells from one CCD patient with allelic RUNX2 deletion and one sex-age matched unaffected individual.

Project description:The goal is to investigate the downstream targets of RUNX2 signaling which are potentially involved in the disease process of Cleidocranial Dysplasia (CCD). RNA-seq was performned to compare the mRNA profiles in human dental pulp cells from one CCD patient with allelic RUNX2 deletion (CCD-011) and sex-age matched unaffected individual(Control). Of 25,643 genes analyzed, 11,039 genes had no detectable signal in both CCD and control samples tested leaving 14,604 genes that were evaluated for differential gene expression. In the detectable genes, 60 transcripts (4.1%) were found to be statistically significantly dysregulated with 63% upregulated and 27% downregulated (fold change ≥ 2; q-value < 0.05).

2017-10-03 | GSE104527 | 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