Genome-wide profile of RBPJ and differential H3K27ac profile upon treatment with HDAC-inhibitor apicidin.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA490346 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7819360_1.fastq.gz | Fastqsanger.gz | |||
| SRR7819360_2.fastq.gz | Fastqsanger.gz | |||
| SRR7819361_1.fastq.gz | Fastqsanger.gz | |||
| SRR7819361_2.fastq.gz | Fastqsanger.gz | |||
| SRR7819362_1.fastq.gz | Fastqsanger.gz |
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Project description:The Notch signaling pathway regulates several differentiation and developmental processes in both pre- and post-natal life and its aberrant regulation leads to diseases, including cancer. Here, we investigated the genome-wide distribution of the transcription factor RBPJ and the differential regulation of H3K27ac upon pharmacological inhibition of histone deacetylase 3 (HDAC3) with apicidin in mouse pre-T (Beko) cells.
2020-02-04 | GSE119797 | GEO
Project description:Investigation of the mechanism by which combined EZH2 and HDAC inhibition kills PC3 prostate cancer cells. Next-generation sequencing was used to identify changes in genome localization of HDAC targets (H3K27ac) and EZH2 targets (H3K27me3) upon treatment with each inhibitor alone or in combination.
2020-05-12 | GSE150336 | GEO
Project description:We achieved local recombination of striatal astrocytes and silenced Notch signalling activity through Rbpj-K depletion. Recombined astrocytes and neural progenitors generated from the striaral glia were FAC sorted and their molecular profile investigated in a scRNAseq experiment performed 5 wpi.
2020-08-01 | GSE153916 | GEO
Project description:We discovered a new class of small molecule inhibitor that disrupts the interaction between NOTCH and RBPJ, which is the main transcriptional effector of NOTCH signaling. RBPJ Inhibitor-1 (RIN1) also blocked the functional interaction of RBPJ with SHARP, a scaffold protein that forms a transcriptional repressor complex with RBPJ in the absence of NOTCH signaling. RIN1 induced changes in gene expression resembled siRNA silencing of RBPJ rather than inhibition at the level of NOTCH itself. RIN1 inhibits RBPJ in its repressing and activating contexts.
2019-07-18 | GSE134401 | GEO
Project description:Notch signalling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighbouring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and together with the transcription factor moiety of Notch (NICD) it regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole genome binding profiles were generated for RBPJ, its coactivator p300, NICD and the histone H3 modifications H3K4me3, H3K4me1 and H3K27ac in myogenic cells under active or inhibitory Notch signalling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300, and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signalling mediate their activities and consequently impact on cell fate decisions. ChIP (chromatin immunoprecipitation) is followed by deep sequencing to generate genome-wide patterns of RBP-J binding in mouse C2C12 cells under various conditions. Cells were either Notch activated by exposure to immobilized ligand or by overexpression of NICDGFP, or Notch inhibited by treatment with DAPT. Notch activation and inhibition treatments were applied for 6h and 24h. In addition to RBP-J, p300 and NICDGFP were profiled by ChIP-Seq and gene expression was assessed by RNA-Seq.
2013-05-13 | E-GEOD-37184 | biostudies-arrayexpress
Project description:Enhancers are fundamental to gene regulation. Post-translational modifications by the small ubiquitin-like modifiers (SUMO) modify chromatin regulation enzymes, including histone acetylases and deacetylases. However, it remains unclear whether SUMOylation regulates enhancer marks, acetylation at the 27th lysine residue of the histone H3 protein (H3K27Ac). We hypothesize that SUMOylation regulates H3K27Ac. To test this hypothesis, we performed genome-wide ChIP-seq analyses. We discovered that knockdown (KD) of the SUMO activating enzyme catalytic subunit UBA2 reduced H3K27Ac at most enhancers. Bioinformatic analysis revealed that TFAP2C-binding sites are enriched in enhancers whose H3K27Ac was reduced by UBA2 KD. ChIP-seq analysis in combination with molecular biological methods showed that TFAP2C binding to enhancers increased upon UBA2 KD or inhibition of SUMOylation by a small molecule SUMOylation inhibitor. However, this is not due to the SUMOylation of TFAP2C itself. Proteomics analysis of TFAP2C interactome on the chromatin identified histone deacetylation (HDAC) machinery. TFAP2C KD reduced HDAC binding to chromatin and increased H3K27Ac marks at enhancer regions, suggesting that TFAP2C is involved in recruiting HDAC. Taken together, our findings provide important insights into regulation of enhancer marks by SUMOylation.
2024-04-13 | PXD045644 | Pride
Project description:BRIN-BD11 pancreatic beta cell mRNA profile upon treatment with Class1 HDAC inhibitor MS-275
| PRJNA578636 | ENA
Project description:Notch signalling plays crucial roles in mediating cell fate choices in all metazoans largely by specifying the transcriptional output of one cell in response to a neighbouring cell. The DNA-binding protein RBPJ is the principle effector of this pathway in mammals and together with the transcription factor moiety of Notch (NICD) it regulates the expression of target genes. The prevalent view presumes that RBPJ statically occupies consensus binding sites while exchanging repressors for activators in response to NICD. We present the first specific RBPJ chromatin immunoprecipitation and high-throughput sequencing study in mammalian cells. To dissect the mode of transcriptional regulation by RBPJ and identify its direct targets, whole genome binding profiles were generated for RBPJ, its coactivator p300, NICD and the histone H3 modifications H3K4me3, H3K4me1 and H3K27ac in myogenic cells under active or inhibitory Notch signalling conditions. Our results demonstrate dynamic binding of RBPJ in response to Notch activation at essentially all sites co-occupied by NICD. Additionally, we identify a distinct set of sites where RBPJ recruits neither NICD nor p300, and binds DNA statically, irrespective of Notch activity. These findings significantly modify our views on how RBPJ and Notch signalling mediate their activities and consequently impact on cell fate decisions.
2013-05-13 | GSE37184 | GEO
Project description:Methods: We performed mRNA sequence analysis by deep sequencing, in triplicate, using Illumina HiSeq to assess the impact of Class1 HDAC inhibitor MS-275 in regulating gene expression in BRIN-BD11 pancreatic beta cells. The transcriptome libraries were constructed using the NEB adapters and were sequenced on at 150 nucleotide read length using the paired-end chemistry. The raw reads were subjected to Adapter and low quality reads removal by Trimmomatic -0.36v. The sequence reads that passed quality filters was mapped to the Rattus_norvegicus Rnor_6.0 using STAR , counted using feature count module of sub reads package and was normalized in DESeq2-3. Differentially expressed genes were selected based on log2-ratio change with p-value <0.05 (Student‘s t test, unpaired). Hierarchical clustering was performed with the programs Cluster (uncentered correlation; average linkage clustering) and Treeview. Results: We mapped 136,002,940 (136 million reads) reads per sample to rat genome (Rnor_6.0) and observed 97% alignment to the reference rat genome. We found that 1858 genes were up regulated and 624 genes got down regulated on MS-275 treatment (log fold change ≥±2 p value < 0.05). Inference: Gene ontology reveals that the upregulated pathways upon MS-275 treatment include endocytosis, cAMP signaling, insulin secretion, Wnt signaling PI3K-Akt signaling and thermogenesis while the downregulated genes include histone modification, chromosome organization and cell cycle regulation. The study represents first detailed mRNA profiling of BRIN-BD11 pancreatic beta cell in context of modulation of expression upon treatment with Class1 HDAC inhibitor MS-275.
2019-10-22 | GSE139147 | GEO
Project description:The transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses was observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch as well as T-cell polarization into TH2 effector cells. The observed phenotype was environment-dependent and could be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopted open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing footprint of transcription factor Gata-3. The over-expression of Ilt3 rendered Rbpj-deficient Treg cells incompatible to specifically restrain TH2 responses, finally leading to severe and fatal lymphoproliferative disease.
2019-01-31 | GSE119164 | GEO