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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Autores principales: Binhua Tang, Yufan Zhou, Chiou-Miin Wang, Tim H.-M. Huang, Victor X. Jin
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Lenguaje:EN
Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/b597d3a6847f4b45bc16c451c33629b7
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
description 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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