Regulation of alternative splicing by histone modifications.
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.
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Reini F
RF
Luco
Qun
Q
Pan
Kaoru
K
Tominaga
Benjamin J
BJ
Blencowe
Olivia M
OM
Pereira-Smith
Tom
T
Misteli
D017398:Alternative Splicing; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005091:Exons; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism; D011467:Prostate / Q000166:cytology; D011485:Protein Binding; D012322:RNA Precursors / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D006657:Histones; C470833:MORF4L1 protein, human; D012322:RNA Precursors; D014157:Transcription Factors; D038941:Polypyrimidine Tract-Binding Protein; D011495:Histone-Lysine N-Methyltransferase; C521636:SETD2 protein, human; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2