Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns
Abstract 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 re...
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Nature Portfolio
2017
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oai:doaj.org-article:b597d3a6847f4b45bc16c451c33629b72021-12-02T11:53:01ZIntegration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns10.1038/s41598-017-03837-z2045-2322https://doaj.org/article/b597d3a6847f4b45bc16c451c33629b72017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03837-zhttps://doaj.org/toc/2045-2322Abstract 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.Binhua TangYufan ZhouChiou-Miin WangTim H.-M. HuangVictor X. JinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Binhua Tang Yufan Zhou Chiou-Miin Wang Tim H.-M. Huang Victor X. Jin Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
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Abstract 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. |
format |
article |
author |
Binhua Tang Yufan Zhou Chiou-Miin Wang Tim H.-M. Huang Victor X. Jin |
author_facet |
Binhua Tang Yufan Zhou Chiou-Miin Wang Tim H.-M. Huang Victor X. Jin |
author_sort |
Binhua Tang |
title |
Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
title_short |
Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
title_full |
Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
title_fullStr |
Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
title_full_unstemmed |
Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
title_sort |
integration of dna methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns |
publisher |
Nature Portfolio |
publishDate |
2017 |
url |
https://doaj.org/article/b597d3a6847f4b45bc16c451c33629b7 |
work_keys_str_mv |
AT binhuatang integrationofdnamethylationandgenetranscriptionacrossnineteencelltypesrevealscelltypespecificandgenomicregiondependentregulatorypatterns AT yufanzhou integrationofdnamethylationandgenetranscriptionacrossnineteencelltypesrevealscelltypespecificandgenomicregiondependentregulatorypatterns AT chioumiinwang integrationofdnamethylationandgenetranscriptionacrossnineteencelltypesrevealscelltypespecificandgenomicregiondependentregulatorypatterns AT timhmhuang integrationofdnamethylationandgenetranscriptionacrossnineteencelltypesrevealscelltypespecificandgenomicregiondependentregulatorypatterns AT victorxjin integrationofdnamethylationandgenetranscriptionacrossnineteencelltypesrevealscelltypespecificandgenomicregiondependentregulatorypatterns |
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1718394947991764992 |