combinations of histone modifications mark exon inclusion levels组蛋白修饰马克外显子的组合包含的水平.pdfVIP

Combinations of Histone Modifications Mark Exon Inclusion Levels 1.¤ ¨ 1. 2 1,3 Stefan Enroth , Susanne Bornelov , Claes Wadelius *, Jan Komorowski * 1The Linnaeus Centre for Bioinformatics, Department of Cell and Molecular Biology, Science for Life Laboratory, Biomedical Center, Uppsala University, Uppsala, Sweden, 2 Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, 3 Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Warszawa, Poland Abstract Splicing is a complex process regulated by sequence at the classical splice sites and other motifs in exons and introns with an enhancing or silencing effect. In addition, specific histone modifications on nucleosomes positioned over the exons have been shown to correlate both positively and negatively with exon expression. Here, we trained a model of ‘‘IF … THEN …’’ rules to predict exon inclusion levels in a transcript from histone modification patterns. Furthermore, we showed that combinations of histone modifications, in particular those residing on nucleosomes preceding or succeeding the exon, are better predictors of exon inclusion levels than single modifications. The resulting model was evaluated with cross validation and had an average accuracy of 72% for 27% of the exons, which demonstrates that epigenetic signals substantially mark alternative splicing. ¨ Citation: Enroth S, Bornelov S, Wadelius C, Komorowski J (2012) Combinations of Histone Modifications Mark Exon Inclusion Levels. PLoS ONE 7(1): e29911. doi:10.1371/journal.pone.0029911 Editor: Cathal Seoighe, National University of Ireland Galway, Ire