Regulation of Alternative Splicing by Histone Modifications

• Published in: Science (American Association for the Advancement of Science) Vol. 327; no. 5968; pp. 996 - 1000
• Main Authors: Luco, Reini F, Pan, Qun, Tominaga, Kaoru, Blencowe, Benjamin J, Pereira-Smith, Olivia M, Misteli, Tom
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 19.02.2010; The American Association for the Advancement of Science
• Subjects: Alternative Splicing; Biological and medical sciences; Cell Line; Cellular biology; Chromatin; Chromatin - metabolism; Down regulation; Epithelial Cells - metabolism; Exons; Fundamental and applied biological sciences. Psychology; Gene expression regulation; HeLa cells; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histones; Histones - metabolism; Humans; Male; Mesenchymal Stem Cells - metabolism; Molecular and cellular biology; Molecular biology; Molecular genetics; Polypyrimidine Tract-Binding Protein - metabolism; Prostate - cytology; Protein Binding; Proteins; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Ribonucleic acid; RNA; RNA Precursors - metabolism; Signatures; Splicing; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing; Human; Posttranslational modification; Alternative splicing; Regulation(control); Histone; Methylation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1184208

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.