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dc.contributor.authorKennedy, Elizabeth M.en_US
dc.contributor.authorGoehring, George N.en_US
dc.contributor.authorNichols, Michael H.en_US
dc.contributor.authorRobins, Chloeen_US
dc.contributor.authorMehta, Divyaen_US
dc.contributor.authorKlengel, Torstenen_US
dc.contributor.authorEskin, Eleazaren_US
dc.contributor.authorSmith, Alicia K.en_US
dc.contributor.authorConneely, Karen N.en_US
dc.date.accessioned2018-07-25T14:22:05Z
dc.date.issued2018en_US
dc.identifier.citationKennedy, Elizabeth M., George N. Goehring, Michael H. Nichols, Chloe Robins, Divya Mehta, Torsten Klengel, Eleazar Eskin, Alicia K. Smith, and Karen N. Conneely. 2018. “An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells.” BMC Genomics 19 (1): 476. doi:10.1186/s12864-018-4842-3. http://dx.doi.org/10.1186/s12864-018-4842-3.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:37298265
dc.description.abstractBackground: Gene expression can be influenced by DNA methylation 1) distally, at regulatory elements such as enhancers, as well as 2) proximally, at promoters. Our current understanding of the influence of distal DNA methylation changes on gene expression patterns is incomplete. Here, we characterize genome-wide methylation and expression patterns for ~ 13 k genes to explore how DNA methylation interacts with gene expression, throughout the genome. Results: We used a linear mixed model framework to assess the correlation of DNA methylation at ~ 400 k CpGs with gene expression changes at ~ 13 k transcripts in two independent datasets from human blood cells. Among CpGs at which methylation significantly associates with transcription (eCpGs), > 50% are distal (> 50 kb) or trans (different chromosome) to the correlated gene. Many eCpG-transcript pairs are consistent between studies and ~ 90% of neighboring eCpGs associate with the same gene, within studies. We find that enhancers (P < 5e-18) and microRNA genes (P = 9e-3) are overrepresented among trans eCpGs, and insulators and long intergenic non-coding RNAs are enriched among cis and distal eCpGs. Intragenic-eCpG-transcript correlations are negative in 60–70% of occurrences and are enriched for annotated gene promoters and enhancers (P < 0.002), highlighting the importance of intragenic regulation. Gene Ontology analysis indicates that trans eCpGs are enriched for transcription factor genes and chromatin modifiers, suggesting that some trans eCpGs represent the influence of gene networks and higher-order transcriptional control. Conclusions: This work sheds new light on the interplay between epigenetic changes and gene expression, and provides useful data for mining biologically-relevant results from epigenome-wide association studies. Electronic supplementary material The online version of this article (10.1186/s12864-018-4842-3) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s12864-018-4842-3en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006777/pdf/en
dash.licenseLAAen_US
dc.subjectDNA methylationen
dc.subjectGene expressionen
dc.subjectTranscriptional regulationen
dc.subjectBlood cellsen
dc.titleAn integrated -omics analysis of the epigenetic landscape of gene expression in human blood cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalBMC Genomicsen
dash.depositing.authorKlengel, Torstenen_US
dc.date.available2018-07-25T14:22:05Z
dc.identifier.doi10.1186/s12864-018-4842-3*
dash.contributor.affiliatedKlengel, Torsten


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