Alternative splicing decouples local from global PRC2 activity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA927240 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23216000.fastq.gz | Fastqsanger.gz | |||
| SRR23216001.fastq.gz | Fastqsanger.gz | |||
| SRR23216002.fastq.gz | Fastqsanger.gz | |||
| SRR23216003.fastq.gz | Fastqsanger.gz | |||
| SRR23216004.fastq.gz | Fastqsanger.gz |
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Project description:PRC2 mediates epigenetic maintenance of gene silencing in eukaryotes via methylation of H3K27. This complex interacts with sets of accessory factors forming two distinct subtypes (PRC2.1 and PRC2.2) that differ in their action and chromatin targeting mechanisms. However, the underlying molecular mechanisms orchestrating PRC2 assembly are not yet understood. Here, we report the identification of an alternative splicing event involving that alternative splicing of the PRC2 core component SUZ12 exon 4 which generates two isoforms coexisting in the same cell in virtually all tissues and developmental stages. Skipping this exon generates a previously uncharacterized isoform (SUZ12S) that forces the formation of the PRC2.1 subtype and favors PRC2 dimerization. Our results suggest that while SUZ12L is needed for maintenance of global H3K27 methylation levels, While SUZ12S is necessary and sufficient to ensure correct repression of Polycomb target genes via promoter-proximal H3K27me3 deposition, the full-length SUZ12L isoform is needed for maintenance of global H3K27 methylation levels. Lastly, we show that mouse embryonic stem cells lacking either of the two isoforms display impaired exit from pluripotency upon differentiation stimulus. Our findings thus reveal evidence for the existence of a physiological mechanism regulating PRC2 assembly and higher order interactions, with an impact on H3K27 methylation and gene repression.
2024-03-18 | GSE223666 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE23513: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (HJAY) GSE23514: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (Exon array) Refer to individual Series
2010-09-01 | E-GEOD-23522 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25287: Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation (expression) GSE25494: Global impact of RNA polymerase II elongation inhibition on alternative splicing regulation (ChIP-Seq) Refer to individual Series
2010-12-09 | E-GEOD-25495 | biostudies-arrayexpress
Project description:We analyzed alternative splicing with Shh medulloblastoma. This dataset contains bam files of whole genome sequencing from 4 cases. Genomic DNA was isolated from both tumor and matched control specimens. We performed whole genome sequence on Illumina Hiseq.
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Project description:Global alternative splicing analysis of cryptic splicing suppressors in C. elegans
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Project description:The rate of RNA polymerase II (pol II) elongation can influence splice site selection in nascent transcripts, yet the extent and physiological relevance of this kinetic coupling between transcription and alternative splicing is not well understood. We performed experiments to perturb pol II elongation and then globally compared alternative splicing patterns with genome-wide pol II occupancy. RNA binding and RNA processing functions were significantly enriched among the genes with pol II elongation inhibition-dependent changes in alternative splicing. Under conditions that interfere with pol II elongation, including cell stress, increased pol II occupancy was detected in the intronic regions flanking the alternative exons in these genes, and these exons generally became more included. A disproportionately high fraction of these exons introduced premature termination codons that elicited nonsense-mediated mRNA decay (NMD), thereby further reducing transcript levels. Our results provide evidence that kinetic coupling between transcription, alternative splicing and NMD affords a rapid mechanism by which cells can respond to changes in growth conditions, including cell stress, to coordinate the levels of RNA processing factors with mRNA levels. In order to identify alternative splicing events influenced by changes in pol II elongation, we performed quantitative alternative splicing microarray profiling (Pan et al., 2004 (PMID 15610736); Shai et al., 2006 (PMID 16403798)) of RNA isolated from stimulated Jurkat T lymphoma cells, cultured separately in the presence or absence of two different drugs that can inhibit pol II elongation: 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole (DRB) and camptothecin.
2010-12-09 | E-GEOD-25287 | biostudies-arrayexpress
Project description:Alternative splicing is considered a major mechanism for creating multicellular diversity from a limited repertoire of genes. Different isoforms can be produced at the same time in the same cell type and their ratios can be the same or different between divergent genotypes. Here, we studied genetic variation in alternative splicing patterns in a large recombinant inbred population of C. elegans, using whole-genome tiling arrays. This experiment allowed us to detect heritable differences in gene expression with exquisite sensitivity and resolution, and we detected 435 genes with substantial heritable variation for at least one exon. Nonetheless, we find only a very small number of examples of heritable variation in alternative splicing (22 transcripts), and most of these genes co-localize with the associated genomic loci. This is in striking contrast to earlier observations in humans, which showed much less genetic robustness. C. elegans recombinant inbred lines were generated and genotyped as described in (Li et al. 2006). mRNA was isolated from 60 RILs reared under standard condition and hybridized to Affymetrix 1.0 C. elegans tiling arrays. The hybridization was done by ServiceXS (Leiden, The Netherlands).
2011-01-01 | E-GEOD-15778 | biostudies-arrayexpress
Project description:RBM39 is extensively involved in alternative splicing of RNA and helps regulate transcript levels. RBM39 may modulate alternative splicing similarly to U2AF65 by either directly binding to RNA or recruiting other splicing factors, such as U2AF65.
2016-09-13 | GSE86846 | GEO
Project description:Background: Despite the prevalence and biological relevance of both signalling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signalling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis of changes in alternative splicing using splicing-sensitive microarrays, induced by activation of two distinct signalling pathways, insulin and wingless, in Drosophila cells in culture. Results: Alternative splicing changes induced by insulin affect more than 150 genes and more than 50 genes are regulated by wingless activation. About 40% of the genes showing changes in alternative splicing also show regulation of mRNA levels, suggesting distinct but also significantly overlapping programs of transcriptional and posttranscriptional regulation. Distinct functional sets of genes are regulated by each pathway and, remarkably, a significant overlap is observed between functional categories of genes regulated transcriptionally and at the level of alternative splicing. Functions related with carbohydrate metabolism and cellular signalling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5â splice sites. Conclusion: Taken together, our data indicate that signalling cascades trigger pathway-specific and biologically coherent regulatory programs of alternative splicing regulation. They also reveal that alternative splicing can provide a novel molecular mechanism for cross-talk between different signalling pathways. To monitor transcriptional and alternative splicing changes induced by activation of the insulin and wingless pathways, a custom-designed microarray platform was employed featuring probes for all Drosophila genes for which different mRNA isoforms generated by alternative splicing have been described (see Blanchette M, Green RE, Brenner SE, Rio DC: Global analysis of positive and negative pre-mRNA splicing regulators in Drosophila. Genes Dev 2005, 19(11):1306-1314.). Three biological replicates of total RNA isolated after pathway activation or controls (untreated cells for insulin, control dsRNA for wingless) were purified, reverse transcribed into cDNA and labelled with Cy5 or Cy3 fluorochromes and the cDNA was hybridized to the microarray,
2010-05-06 | E-GEOD-14085 | biostudies-arrayexpress