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Next Generation Sequencing for Genome-wide Maps of DNA Methylation, ChIP-seq and RNA-seq in Liver Cells

ABSTRACT: Aberrant DNA methylation is a distinguished feature of cancer. We introduce a novel method of Guide Positioning Sequencing (GPS) for precisely detecting whole genome DNA methylation and applied GPS as well as ChIP-seq and RNA-seq in normal liver cells and hepatoma cell lines to find how abberant DNA-methylation affect gene expression and cell identity during tumorigenesis and metastasis. We systematically found that the methylation difference between genebody and promoter is an effective predictor for gene expression with a correlation coefficient of 0.7. Moreover, Methylation boundary shift (MBS) in the promoter or enhancer is also capable of modulating the expression categorized within immune response process and tumor metabolism. Furthermore, aberrant DNA methylation is related to the gain or loss of tissue specific enhancer which is responsible for altering cell identity during liver cancer development and metastasis prone to the lung.

ORGANISM(S): Homo sapiens

PROVIDER: GSE92328 | GEO | 2018/12/17

REPOSITORIES: GEO

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Project description:Age-related methylation changes have been identified in various tissues and organisms, yet the underlying DNA methylation alterations in muscle aging process have not been clearly clarified. Whilst, many studies revealed that the structural and functional changes in skeletal muscle during aging process started from the mid-point of lifespan. In this study, we used pigs aged 0.5 year and 7 years, representing young and middle-aged periods. Using methylated DNA immunoprecipitation sequencing, we performed comprehensive genome-wide DNA methylation profiling for longissimus dorsi muscle in young and middle-aged pigs. We found more genes showed differently methylated in genebody. In details, 185 human ortholog genes contained DMRs that located in the promoter region, while 657 genes and 1063 genes with DMRs in gene body showed hypermethylation and hypomethylation in MA pigs, respectively. From the gene enrichment analysis, genebody hypermethylated genes showed significant enrichment for several molecular functions such as M-bM-^@M-^XGTPase regulator activityM-bM-^@M-^Y, M-bM-^@M-^XATP bindingM-bM-^@M-^Y and M-bM-^@M-^Xprotein kinase activityM-bM-^@M-^Y. Notably, genebody hypomethylated genes showed significant enrichment for various proteolysis and protein catabolic process. However, genes with DMR in their promoter region were not significantly enriched in any biology process. Proteolysis-associated genes, such as FOXO3 and FGFR1, showed different genebody methylation and mRNA expression level in two age groups, which may contribute to muscle atrophy during aging. Especially, other tumorigenesis-associated genes including GPI and GRB2, exhibited increasing mRNA level in middle-aged pigs, suggesting the possible higher risk of having cancer in human middle-aged period. Our results will serve as a valuable resource in aging studies, promote pig as a model organism for human aging research and accelerate the considerable development of comparative animal models in aging research. We collected the longissimus dorsi muscles tissue from Jinhua pigs which aged 0.5 year and seven years and study the genome-wide DNA methylation difference and the genome-wide gene expression profile between the two age periods. This submission represents transcriptome component of study.

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Next Generation Sequencing for Genome-wide Maps of DNA Methylation, ChIP-seq and RNA-seq in Liver Cells

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