dateReleased: |
03-08-2015
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description: |
The global impact of DNA methylation on alternative splicing is largely unknown. Using a genome-wide approach in wild-type and methylation-deficient embryonic stem cells, we found that DNA methylation can act both as an enhancer and as a silencer of splicing, and affects the splicing of more than 20% of alternative exons. These exons are characterized by distinct genetic and epigenetic signatures. Alternative splicing regulation of a subset of these exons can be explained by Heterochromatin protein 1 (HP1), which silences or enhances exon recognition in a position-dependent manner. We constructed an experimental system using site-specific targeting of a methylated/unmethylated gene, and demonstrate a direct causal relationship between DNA methylation and alternative splicing. HP1 regulates this gene’s alternative splicing in a methylation-dependent manner by recruiting splicing factors to its methylated form. Our results demonstrate DNA methylation's significant global influence on mRNA splicing, and identify a specific mechanism of splicing regulation mediated by HP1. BS-seq on WT mouse ES cells (2 replicates), MNase-seq on WT and TKO cells (3 replicates), mRNA-seq on WT and TKO cells as well as HP1 knock-down cells (2 replicates for each sample)
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privacy: |
not applicable
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aggregation: |
instance of dataset
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ID: |
E-GEOD-64910
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refinement: |
raw
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alternateIdentifiers: |
64910
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keywords: |
functional genomics
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dateModified: |
03-16-2015
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availability: |
available
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types: |
gene expression
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name: |
Mus musculus
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-64910/E-GEOD-64910.raw.1.zip![]() |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-64910/E-GEOD-64910.processed.1.zip![]() |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64910 |
storedIn: |
Gene Expression Omnibus
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qualifier: |
not compressed
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format: |
HTML
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accessType: |
landing page
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primary: |
true
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authentication: |
none
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authorization: |
none
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abbreviation: |
EBI
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homePage: | http://www.ebi.ac.uk/ |
ID: |
SCR:004727
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name: |
European Bioinformatics Institute
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homePage: | https://www.ebi.ac.uk/arrayexpress/ |
ID: |
SCR:002964
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name: |
ArrayExpress
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