Analysis Of Histone Modification Patterns In Cassette Exons

Alternative splicing(AS)is an important biological process of gene expression,which can generate multiple transcripts products from a single gene.It was found that AS participates in a series of biological processes.Although lots of researches have been carried out,the regulatory mechanisms of AS remain unclear.Results of cotranscriptional RNA processing analysis demonstrated that,except for trans-and cisacting elements in the genome,AS was also regulated by histone modifications.With the advancement of next generation sequencing technology,a massive amount of epigenetic data has been generated,which provide valuable resources for the researches on AS.By calculating the inclusion rate of alternatively spliced exons in the exon skipping pattern,the cassette exons in human embryonic stem cell line(H1)and embryonic lung fibroblasts cell line(IMR90)were obtained.By analyzing the histone modification data,distinct patterns for histone methylation and acetylation were observed in excluded and included exons in H1 and IMR90 cell lines.Accordingly,a Random Forest based model was built to classify the excluded and included exons,in which the exons were encoded by using histone modifications.It was found that the proposed model obtained accuracies of 0.607 and 0.611 in H1 and IMR90 cell lines,respectively.In addition,the Pearson correlation coefficients were also calculated among different kinds of histone modifications.It was found that the weak correlations were observed between histone methylation and acetylation modifications,and strong correlations were observed among the same kind of modifications.Based on the correlationships of histone modifications,the Bayesian network was built to deduce their casual relationships in the process of RNA alternative splicing.Both common and distinct topologies were observed in cassette exons and surrounding introns.This result indicates that RNA alternative splicing might be regulated by the combinatorial patterns of histone modifications.Figure 29;Table 5;Reference 71...