Inferring causal relationships among histone modifications in exon skipping event

Abstract

Alternative splicing is a crucial process of gene expression. Over 90% multi-exonic genes in human genome undergo alternative splicing. Although the splicing code has been proposed, it still couldn't satisfactorily explain the tissue-specific alternative splicing. Results of co-transcriptional RNA processing analysis demonstrated that, except for trans- and cis-acting elements, histone modifications also play a role in alternative splicing. In the present work, we analyzed the associations among 27 kinds of histone modifications in H1 human embryonic stem cell. In order to illustrate the casual relationships between histone modification and alternative splicing, we built the Bayesian network and validated its robustness by using cross validation test. In addition to the combinatorial patterns, distinct histone modification patterns were also observed in the alternative spliced exons and surrounding intron regions, indicating that histone modifications could substantially mark alternative splicing.

Keywords: Alternative splicing; Bayesian network; Causal relationship; Exon skipping; Histone modification.