Integrative Analysis Of Second Generation Sequencing For Transcriptome And Mechanisms Of Transcriptional Regulation In Mammals

The spectacular challenge in post-genomic research is how to elucidate linkages between genotypes and phenotypes. With fast-updated sequencing technology, transcriptomic research has focused on whole genomics situation instead of some special genes. Applications of high-throughput, short sequence tag-based approaches (such as SOLiD and Solexa) allow us to interrogate transcriptome and epigenetic regulations genome-wide, to discriminate switch-signals for differentiation and development process in multiple levels, and to understand mutual evolution between regulation systems and genome sequences.We acquired a set of genome-wide nucleosome distribution and transcriptomic data from mouse tissues based on ChIP (H3)-seq and RNA-seq. We identified particularly conserved nucleosome-space occupancy (NO) patterns among three mouse tissues—cerebrum, testis, and ESCs. The NO variations among chromosomes are closely associated with regional DNA transcript activity. High density array of nucleosome can provide the target for other related regulation systems and enhance DNA sensitive to regulations by NO mechanism. Furthermore, we integrated the transcriptomic data, NO patterns and SNP data to explain the period mutation patterns and the importance of transcription-coupled repair in mammal genome. Finally, using the high-coverage RNA-seq data of multiple mouse and human tissues and cells, we demonstrated that similar with HK genes, TS genes are clustered conservatively in mammalian genomes. The results improve our understanding on special profiles and functions of different tissues.