Abstract
Alternative splicing of pre-mRNA is a prominent mechanism to generate protein diversity, yet its regulation is poorly understood. We demonstrated a direct role for histone modifications in alternative splicing. We found distinctive histone modification signatures that correlate with the splicing outcome in a set of human genes, and modulation of histone modifications causes splice site switching. Histone marks affect splicing outcome by influencing the recruitment of splicing regulators via a chromatin-binding protein. These results outline an adaptor system for the reading of histone marks by the pre-mRNA splicing machinery.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alternative Splicing*
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Cell Line
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Chromatin / metabolism
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Epithelial Cells / metabolism
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Exons
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Histone-Lysine N-Methyltransferase / genetics
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Histone-Lysine N-Methyltransferase / metabolism
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Histones / metabolism*
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Humans
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Male
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Mesenchymal Stem Cells / metabolism
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Polypyrimidine Tract-Binding Protein / metabolism
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Prostate / cytology
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Protein Binding
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RNA Precursors / metabolism*
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Receptor, Fibroblast Growth Factor, Type 2 / genetics
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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Chromatin
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Histones
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MORF4L1 protein, human
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RNA Precursors
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Transcription Factors
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Polypyrimidine Tract-Binding Protein
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Histone-Lysine N-Methyltransferase
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SETD2 protein, human
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FGFR2 protein, human
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Receptor, Fibroblast Growth Factor, Type 2