The Systematic Analysis Of Human Promoter And Interaction Network Of Transcription Factor And Splicing Factor

In eukaryote, the gene expression and regulation is a very complicated process which implicated with many nucleic acid sequences and protein regulatory factors. For example, alternative splicing is regulated by many RNA motifs and protein factors. Alternative promoter are widespread in eukaryotic genome and increase the complexity of gene expression and regulation. The epigenetic information, such as nucleosome positioning, DNA methylation and histone modification, may have a role on the selection of alternative promoter. The study of promoter structure and function is helpful for understanding the mechanisms of transcriptional regulation and disease. Transcription factor and splicing factor are important regulation proteins in gene expression and regulation. Transcription is initiated by transcription factor which recognizes and binds to promoter. Splicing factor controls the splicing process of pre-mRNA. Transcription and splicing process is mutual coupling. The coupling mechanism between transcription and splicing is not clear. The systematic analysis of human promoter, human protein interaction network of transcription factor and splicing factor are helpful for understanding the eukaryotic gene expression regulation and disease therapy.Promoter data were obtained from the DBTSS and were divided into alternative promoter and constitutive promoter. Base on GC content, frequency of dinucleotides, DNA information content, DNA deformation energy, nucleosome occupancy, DNA methylation and histone modification, we analyzed the sequence characteristic of human promoter. As a comparison, the promoter of mouse, zebrafish and schyzon were also analyzed involved with GC content and frequency of dinucleotides. The human protein interaction network of transcription factor and splicing factor was constructed based on SpliceAid F, TFclass, HPRD, Biogrid, DIP, Intact and HINT database. Some features were analyzed, such as degree, clustering coefficient, betweeness centrality, etc. The number of transcription factor connected to splicing factor or other proteins were calculated statistically. The interaction bias of proteins was evaluated by using protein-protein interaction relative bias.The calculated results of human, mouse, zebrafish and schyzon promoter showed that, the sequence features are more similarities between human and mouse promoter. The GC content of alternative promoter is higher than constitutive promoter. The dinucleotides frequency difference is not significantly between alternative promoter and constitutive promoter.The systemtic analysis of human promoter indicated that DNA information content is not significantly different between alternative promoter and constitutive promoter. However, the base distribution is regularly and compose of dinucleotides have relevance. In euchromosomes, the DNA deformation energy and nucleosome occupancy of alternative promoter is higher than that in constitutive promoter, and the two features are lower neighboring transcription start site, but the rule does not exist in sex chromosomes. The level of DNA methylation is low in complicated alternative promoter and sex chromosomes. There is no significantly different at the level of methylation between alternative promoter and constitutive promoter, in poopsite, the histone modification between alternative promoter and constitutive promoter have some difference.The analysis of interaction network between transcription factor and splicing factor showed that transcription factor and splicing factor can coupled each other, which are connected by one, two and three other proteins. The bottleneck proteins account for20%of proteins which directly connect transcription factor and splicing factor. The protein interactions relative bias within transcription factor and splicing factor were larger than that between them.