The Analysis Of Gene Methylation Difference In Different Cell Lines And Tissues And The Correlation Between Sequence Composition And CpG Methylation Level

DNA methylation is one of the most studied epigenetic modifications. It is a chemical process including a methyl group is attached on the number 5 carbon of the cytosine pyrimidine ring catalyzed by DNA methytransferases which is common in a 5’-CG-3’dinucleotide (called CpG). Most vertebrate genomes exist clusters of methylated cytosine nucleotides, mainly in gene 5’non-coding region. The methylation status of cytosines in CpGs influences protein-DNA interactions and chromatin structure and stability, and consequently plays a vital role in the regulation of biological processes such as transcription, X chromosome inactivation, genomic imprinting. Recent studies revealed that DNA methylation patterns in mammals are tissue-or cell line-specific. However, our understanding of the regulatory role of those specific DNA methylations remains incomplete. Therefore, the analysis and comparison of gene methylation characteristic between tissues, cell types is essential for understanding the mechanism of DNA methylation in different biological processes.Based on Refseq gene annotation downloaded from the UCSC Genome Browser,21740 genes with more than two exons were extracted from total 49611 genes in RefSeq tracks. The Bisulfite-Seq data downloaded from NCBI Database Browser and the value denotes the methylation degree for each CpG site is between 0 and 1. For any gene, we consider it is made up of six functional regions include transcription start site region(TSSR), first exon (FE), medium exon region(MER), intron region(IR), last exon(LE), and transcription termination site region(TTSR). The methylation differences of 6 regions were analyzed and compared across 9 cell lines and 15 tissues. We found the methylation level has difference between 6 regions. Then, we proposes two methods to identify different methylation gene (DMG) by the parameter of increment of diversity or Euclidean distance and obtained some DMGs. Meanwhile, the housekeeping genes maintained a low methylation level which is necessary to maintain basic cellular metabolism.For understanding the effect of adjacent sequence on methylation degree of CpG site, the segment with 23 nucleotides was extracted and its centre is cytosine. The analysis of sequence feature for 11 sets of CpG site with different methylation degree illustrated the methylation degree of CpG site is associated with DNA base composition upstream and downstream. The CpG site with the lower methylation level has the more C, G or CC, GG, GC, CG. By MEMEmotif analysis, we obtained their specific motif for different CpG sets with higher and lower methylation level. By calculating sequence energy, relative stability and flexibility of CpG sites, we found the increase of methylation value, its energy, relative stability and flexibility gradually reduced.