Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MCF10A cells expressing empty vector, siRNA-resistant wild-type and siRNA-resistant catalytically dead TIP60 treated with control or TIP60 siRNA

ABSTRACT: Alternative splicing of RNA transcripts can result in a multitude of variations from the genome. Since splicing can occur co-transcriptionally, chromatin structure has been reported to affect the choice of a splice site. TIP60 is a haploinsufficient tumor suppressor gene that is frequently downregulated in cancers. Since TIP60 is a writer of histone and non-histone modifications, we investigated TIP60’s role in modulating alternative splicing. RNA sequencing was performed in TIP60-depleted MCF10A cells and with cells rescued with wild-type or catalytically inactive TIP60. The majority of the differential splicing events were skipped exon events, including exon 25 skipping event of ITGA6. To identify the splicing factor that regulates this event, a siRNA screen of 77 splicing factors was employed. TIP60 depletion results in an increase in the ITGA6 isoform that lacks exon 25 and the siRNA screen identified ESRP2 to regulate splicing of ITGA6 exon 25. This study suggests that alternative splicing of ITGA6 exon 25 is regulated by the TIP60-ESRP2 axis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE152863 | GEO | 2023/06/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The epithelial splicing factors ESRP1 and ESRP2 positively and negatively regulate alternative splicing events

Project description:Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are recently discovered epithelial-specific RNA-binding proteins that promote splicing of the epithelial variant of the FGFR2, ENAH, CD44, and CTNND1 transcripts. To catalogue a larger set of splicing events under the regulation of the ESRPs, we profiled splicing changes induced by RNA interference-mediated knockdown of ESRP1 and ESRP2 expression in a human epithelial cell line using the splicing-sensitive Affymetrix Exon ST1.0 Arrays. Analysis of the microarray data using the previously described MADS tool resulted in the identification of over a hundred candidate ESRP-regulated splicing events. We were able to independently validate 37 of these targets by RT-PCR. The ESRP-regulated events encompass all known types of alternative splicing events. Importantly, a number of these regulated splicing events occur in gene transcripts that encode proteins with well-described roles in the regulation of actin cytoskeleton organization, cell-cell adhesion, cell polarity, and cell migration. In sum, this work reveals a novel list of transcripts differentially spliced in epithelial and mesenchymal cells, implying that coordinated alternative splicing plays a critical role in determination of cell type identity. Keywords: control / knockdown comparison Short interfering knockdown of ESRP1 and ESRP2 in human PNT2 prostatic epithelium cells was performed as described before (Warzecha et al., 2009, Molecular Cell 33:591-601). The efficiency of ESRP1 and ESRP2 knockdown was monitored by quantitative RT-PCR as described before (Warzecha et al., 2009, Molecular Cell 33:591-601). In all cases the efficiency of the knockdown was close to 80%. We conducted Exon array profiling on RNAs from four siESRP1/2-treated samples and four siGFP controls.

2010-08-18 | E-GEOD-17468 | biostudies-arrayexpress

RNA-sequencing in OS-RC-2 cells under the knockdown of Arkadia or ESRP2

Project description:Tumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC). Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC. Expression of mRNA in a ccRCC cell line OS-RC-2 under the knockdown of Arkadia or ESRP2. Knock-down of ESRP2 was confirmed by RT-PCR because of low expression of ESRP2 which resulted in non-quantitative FPKM value.

2015-08-01 | E-GEOD-66741 | biostudies-arrayexpress

Expression analysis of HCT116 cells transfected using Tip60 or p400-targetting siRNA

Project description:Investigation of whole genome gene expression level changes in HCT116 cells upon knockdown of Tip60 or p400, compared to control siRNA-transfected cells. Two different siRNA directed against Tip60 were used and experiments were done in duplicate. Same for p400-targetting or control siRNA. Hybridization experiment using total RNA recovered from independent cell cultures of HCT116 transfected using control, Tip60-targetting or p400-targetting siRNA.

2013-11-22 | E-GEOD-45615 | biostudies-arrayexpress

TIP60 complex

Project description:TIP60 complex

| PRJNA312375 | ENA

ESRP2 Regulates A Conserved And Cell-Type-Specific Splicing Program to Support Postnatal Liver Maturation

Project description:Alternative splicing greatly expands the proteomic diversity but its functional impact is often unclear. Here, we identify a highly conserved and temporally coordinated cell-type-specific splicing program, which is activated in part by ESRP2 during postnatal liver development. Consistent with failure of many neonatal-to-adult splicing transitions, Esrp2 null mice exhibit persistent expression of fetal markers and loss of mature hepatocyte characteristics. Conversely, ectopic expression of ESRP2 in immature mouse or human hepatocytes results in a reciprocal switch in splicing. Our findings define an essential role for ESRP2 in generation of conserved repertoires of adult splice isoforms that facilitate postnatal liver maturation. Mouse liver RNA was isolated with Trizol (Invitrogen). Hi-Seq libraries were prepared and paired-end 100bp Illumina sequencing was performed on mouse liver samples from different developmental stages.

2015-11-04 | E-GEOD-67009 | biostudies-arrayexpress

Validation of the expression of clathrin heavy chain muscle isoform including exon 31 at the protein level

Project description:A single exon alternative splicing in the CLTC gene determines clathrin coat organization. This event controls plasticity from clathrin-coated pits to plaques, structures that are essential for muscle fiber function and maintenance

2020-06-19 | PXD018333 | Pride

Determination of a comprehensive alternative splicing regulatory network and the combinatorial regulation by key factors during Epithelial-to-Mesenchymal Transition [ESRP KD]

Project description:Epithelial specific splicing regulatory protein 1 and 2 (ESRP1 and ESRP2) are important regulators of alternative splicing during EMT. To study the alternative splicing events regulated by ESRP1/2 at a genome wide scale, we used lentiviral shRNAs to knockdown ESRP1/2 in H358 cells and performed RNA-seq in biological triplicates. We used lentiviral based shRNAs targeting ESRP1 and ESRP2 to knockdown both regulators in human H358 cells. We harvested total RNA and protein from ESRP1/2 knockdown and control knockdown in biological triplicates. We made cDNA libraries for each replicate and subjected them to RNA-seq.

2016-04-05 | E-GEOD-75489 | biostudies-arrayexpress

Expression analysis of HCT116 cells transfected using Tip60 or p400-targetting siRNA

2013-11-22 | GSE45615 | GEO

RNA-sequencing in OS-RC-2 cells under the knockdown of Arkadia or ESRP2

2015-08-01 | GSE66741 | GEO

ESRP2 Regulates A Conserved And Cell-Type-Specific Splicing Program to Support Postnatal Liver Maturation

2015-11-04 | GSE67009 | GEO