人类基因组跳跃外显子组蛋白修饰特征分析

Analysis of Histone Modification Features on Skipping Exons of Human Genome

可变剪接是调节基因表达和产生蛋白质组多样性的重要机制,研究表明组蛋白修饰能够影响基因的可变剪接。本文基于GM12878和K562两种细胞系的RNA-seq数据,构建了跳跃外显子(SE)的可变剪接数据集(Alternative skipping exon set,简称ASES),包括外显子跳跃(SE_Out),外显子保留(SE_In)和非特异性跳跃外显子(SE_Non_Spec)三种类型的可变剪接事件。通过计算跳跃外显子11种组蛋白修饰水平与剪接百分比Ψ之间的相关性,发现H3K36me3、H3K79me2和H4K20me1的修饰水平与Ψ在SE_Out事件中正相关,在SE_In事件中负相关,表明这三种组蛋白修饰对SE_Out事件起促进作用,对SE_In事件起抑制作用,且组蛋白修饰水平与剪接百分比的相关性随着区域长度的增加而变大。进一步,通过统计发现H3K27ac、H3K79me2和H3K36me3在SE_In、SE_Out和SE_Non_Spec事件上的分布存在较为明显的差异。

Alternative splicing is an important mechanism for generating proteome diversity.Studies have shown that histone modifications(HMs)can regulate alternative splicing.Based on the RNA-seq data of GM12878 and K562 cell lines,the alternative skipping exon set(named ASES)including retained skipping exon(SE_In),skipped exon(SE_Out)and non-specific skipping exon(SE_Non_Spec)events was constructed in the two cell lines.By calculating the Pearson correlation coefficients between the level of 11 HMs and the percentage-spliced-inΨof skipping exons,we found that the correlation of H3 K36 me3,H3 K79 me2 and H4 K20 me1 were positive in the SE_Out events and negative in the SE_In events.The results indicated that these three HMs promote the SE_Out event and inhibit the SE_In event.Meanwhile,the correlation increases as the elongation of the region.Furthermore,we found that the distributions of H3 K27 ac,H3 K79 me2 and H3 K36 me3 on the SE_In,SE_Out and SE_Non_Spec events are significantly different.