Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns. Sci Rep 2017 Jun 15;7(1):3626
Date
06/18/2017Pubmed ID
28620196Pubmed Central ID
PMC5472622DOI
10.1038/s41598-017-03837-zScopus ID
2-s2.0-85020861990 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Despite numerous studies done on understanding the role of DNA methylation, limited work has focused on systems integration of cell type-specific interplay between DNA methylation and gene transcription. Through a genome-wide analysis of DNA methylation across 19 cell types with T-47D as reference, we identified 106,252 cell type-specific differentially-methylated CpGs categorized into 7,537 differentially (46.6% hyper- and 53.4% hypo-) methylated regions. We found 44% promoter regions and 75% CpG islands were T-47D cell type-specific methylated. Pyrosequencing experiments validated the cell type-specific methylation across three benchmark cell lines. Interestingly, these DMRs overlapped with 1,145 known tumor suppressor genes. We then developed a Bayesian Gaussian Regression model to measure the relationship among DNA methylation, genomic segment distribution, differential gene expression and tumor suppressor gene status. The model uncovered that 3'UTR methylation has much less impact on transcriptional activity than other regions. Integration of DNA methylation and 82 transcription factor binding information across the 19 cell types suggested diverse interplay patterns between the two regulators. Our integrative analysis reveals cell type-specific and genomic region-dependent regulatory patterns and provides a perspective for integrating hundreds of various omics-seq data together.
Author List
Tang B, Zhou Y, Wang CM, Huang TH, Jin VXAuthor
Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell LineCell Line, Tumor
CpG Islands
DNA Methylation
Gene Expression Profiling
Gene Expression Regulation
Genomics
High-Throughput Nucleotide Sequencing
Humans
Organ Specificity
Regulatory Sequences, Nucleic Acid
Transcription, Genetic