Constructing Alternative Splicing Data Related With Cell Lines And The Analysis Of Histone Modification Features Around Splicing Sites

Alternative splicing(AS)is an important mechanism for regulating gene expression and increases transcriptome and proteome diversity.Aberrant splicing has been reported to be linked to many diseases.Evidences indicated that histone modification can regulate alternative splicing in humans.Identification of splice sites,detection of alternative splicing events,and analysis of interaction relationship between histone modifications and alternative splicing event are significant in revealing the regulation of pre-mRNA splicing and the mechanisms of alternative splicing.Using TopHat,135332 splice sites and 127167 splice sites were identified in GM12878 and K562.Based on gene annotation information in Ref-seq,three kinds of alternative splicing data are constructed which are exon skipping,alternative donor splice site and alternative acceptor splice site event respectively.As a result,in GM12878,1938 exon skipping events including 945 included model and 193 excluded model,598 alternative donor splice site events including 59 distal model and 83 proximal model and 626 alternative acceptor splice site events including 50 distal model and 89 proximal model are obtained.In K562,1683 exon skipping events including 782 included model and 193 excluded model,607 alternative donor splice site events including 65 distal model and 97 proximal model and 566 alternative acceptor splice site events including 56 distal model and 80 proximal model are obtained.Based on the above data of three alternative splicing types in GM12878 and K562 cell lines,the distribution features of 11 histone modifications is analyzed.For the included and excluded model of exon skipping events,we found that the distribution of H3K79me2 show obvious differences in both cell lines.But,H3K4me2?H3K4me3?H3K9ac and H3K27 ac show differences only in K562.For distal and proximal model of alternative donor splice site events,the distribution of H3K4me1 show obvious differences in both cell lines.But,H2AFZ?H3K9ac?H3K27ac?H3K79me2 and H3K4me3 show differences only in GM12878.For distal and proximal model of alternative acceptor splice site events,the distribution of H3K27ac?H3K4me2 ? H3K4me3 show differences in both cell lines.But,H3K9 ac in GM12878 and H3K79me2 in K562 show differences.Finally,by comparison of alternative splicing events between GM12878 and K562,12 cell-line-specific alternative splicing events are found which are related with 12 genes(SLC25A26,PTK2 B,OSBPL3,XPR1,MAP4K3,SLC9B2,ABI2,MDM4 and ECHDC1,STRN3,EIF4G3 and CELF1).By Gene Ontology(GO)analysis,we found these genes are associated with steroid binding,protein kinase binding,kinase regulator activity,calcium ion binding,RNA binding,translation regulation activity,receptor activity,transporter activity and protein-tyrosine kinase activity.They participate in the regulation of cell proliferation,protein metabolism,signal transduction,steroid metabolism,and nucleic acid metabolism.Among them the CELF1 gene is involved in the regulation of epigenetic regulation.