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- W2940338593 abstract "Splicing of precursor mRNA (pre-mRNA) is an important regulatory step in gene expression. Recent evidence points to a regulatory role of chromatin-related proteins in alternative splicing regulation. Using an unbiased approach, we have identified the acetyltransferase p300 as a key chromatin-related regulator of alternative splicing. p300 promotes genome-wide exon inclusion in both a transcription-dependent and -independent manner. Using CD44 as a paradigm, we found that p300 regulates alternative splicing by modulating the binding of splicing factors to pre-mRNA. Using a tethering strategy, we found that binding of p300 to the CD44 promoter region promotes CD44v exon inclusion independently of RNAPII transcriptional elongation rate. Promoter-bound p300 regulates alternative splicing by acetylating splicing factors, leading to exclusion of hnRNP M from CD44 pre-mRNA and activation of Sam68. p300-mediated CD44 alternative splicing reduces cell motility and promotes epithelial features. Our findings reveal a chromatin-related mechanism of alternative splicing regulation and demonstrate its impact on cellular function." @default.
- W2940338593 created "2019-04-25" @default.
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- W2940338593 date "2019-04-15" @default.
- W2940338593 modified "2023-10-18" @default.
- W2940338593 title "Regulation of alternative splicing by p300-mediated acetylation of splicing factors" @default.
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- W2940338593 doi "https://doi.org/10.1261/rna.069856.118" @default.
- W2940338593 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6573785" @default.
- W2940338593 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30988101" @default.
- W2940338593 hasPublicationYear "2019" @default.
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