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An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells
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-wid...
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Published in: | BMC genomics 2018-06, Vol.19 (1), p.476-476, Article 476 |
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description | 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.
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 |
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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.
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.</description><identifier>ISSN: 1471-2164</identifier><identifier>EISSN: 1471-2164</identifier><identifier>DOI: 10.1186/s12864-018-4842-3</identifier><identifier>PMID: 29914364</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Adolescent ; Adult ; Aged ; Analysis ; Atherosclerosis ; Binding sites ; Biological effects ; Blood ; Blood cells ; Blood Cells - metabolism ; Chromatin ; Cohort Studies ; CpG Islands ; Data mining ; Data processing ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Enhancers ; Enrichment ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Female ; Gene expression ; Gene Expression Profiling ; Gene Ontology ; Genes ; Genetic transcription ; Genomes ; Genomics ; Humans ; Insulators ; Male ; Methylation ; MicroRNAs ; Middle Aged ; miRNA ; Promoters ; Regulatory sequences ; Ribonucleic acid ; RNA ; Studies ; Transcriptional regulation ; Young Adult</subject><ispartof>BMC genomics, 2018-06, Vol.19 (1), p.476-476, Article 476</ispartof><rights>COPYRIGHT 2018 BioMed Central Ltd.</rights><rights>Copyright © 2018. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s). 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-54e3ab9c345df1bb734a6ee19174e176fc38485a9870b3047120a4e3c49ae1543</citedby><cites>FETCH-LOGICAL-c594t-54e3ab9c345df1bb734a6ee19174e176fc38485a9870b3047120a4e3c49ae1543</cites><orcidid>0000-0003-0074-2840</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006777/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2056819352?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29914364$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kennedy, Elizabeth M</creatorcontrib><creatorcontrib>Goehring, George N</creatorcontrib><creatorcontrib>Nichols, Michael H</creatorcontrib><creatorcontrib>Robins, Chloe</creatorcontrib><creatorcontrib>Mehta, Divya</creatorcontrib><creatorcontrib>Klengel, Torsten</creatorcontrib><creatorcontrib>Eskin, Eleazar</creatorcontrib><creatorcontrib>Smith, Alicia K</creatorcontrib><creatorcontrib>Conneely, Karen N</creatorcontrib><title>An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells</title><title>BMC genomics</title><addtitle>BMC Genomics</addtitle><description>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.
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.
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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Atherosclerosis</subject><subject>Binding sites</subject><subject>Biological effects</subject><subject>Blood</subject><subject>Blood cells</subject><subject>Blood Cells - metabolism</subject><subject>Chromatin</subject><subject>Cohort Studies</subject><subject>CpG Islands</subject><subject>Data mining</subject><subject>Data processing</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Enhancers</subject><subject>Enrichment</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Ontology</subject><subject>Genes</subject><subject>Genetic transcription</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Insulators</subject><subject>Male</subject><subject>Methylation</subject><subject>MicroRNAs</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Promoters</subject><subject>Regulatory sequences</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Studies</subject><subject>Transcriptional regulation</subject><subject>Young Adult</subject><issn>1471-2164</issn><issn>1471-2164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkstr3DAQh01padK0f0AvRdBLe3Cql_W4FJbQx0Kg0MdZjOWxV4vX2lp2SP77ytk07Jbig83om8_M6FcUrxm9ZMyoD4lxo2RJmSmlkbwUT4pzJjUrOVPy6dH3WfEipS2lTBtePS_OuLVMCiXPC1gNJAwTdiNM2JAy7oJPBAbo71JIJLZk2iDBfehwwCl40sPQJA97XM6WIsHb_YgphbiYyGbewUDqPsaGeOz79LJ41kKf8NXD-6L49fnTz6uv5fW3L-ur1XXpKyunspIooLZeyKppWV1rIUEhMsu0RKZV64WRpgJrNK0FzZNxCrnHSwvIKikuivXB20TYuv0YdjDeuQjB3Rfi2DkY8wQ9OqXAWG2AtlZJ5DZLjW-qbNS8Fl5k18eDaz_XO2w8DtMI_Yn09GQIG9fFG6coVVrrLHj3IBjj7xnT5HYhLeuAAeOcHKeVZsLqimf07T_oNs5jvoB7ShlmxTHVQR4gDG3M__WL1K0qqYzmVNpMXf6Hyk-D-V7jgG3I9ZOG9ycNmZnwdupgTsmtf3w_ZdmB9WNMacT2cR-MuiWP7pBHl_Poljy6ZZFvjhf52PE3gOIP3n3YGA</recordid><startdate>20180619</startdate><enddate>20180619</enddate><creator>Kennedy, Elizabeth M</creator><creator>Goehring, George N</creator><creator>Nichols, Michael H</creator><creator>Robins, Chloe</creator><creator>Mehta, Divya</creator><creator>Klengel, Torsten</creator><creator>Eskin, Eleazar</creator><creator>Smith, Alicia K</creator><creator>Conneely, Karen N</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0074-2840</orcidid></search><sort><creationdate>20180619</creationdate><title>An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells</title><author>Kennedy, Elizabeth M ; Goehring, George N ; Nichols, Michael H ; Robins, Chloe ; Mehta, Divya ; Klengel, Torsten ; Eskin, Eleazar ; Smith, Alicia K ; Conneely, Karen N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c594t-54e3ab9c345df1bb734a6ee19174e176fc38485a9870b3047120a4e3c49ae1543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Analysis</topic><topic>Atherosclerosis</topic><topic>Binding sites</topic><topic>Biological effects</topic><topic>Blood</topic><topic>Blood cells</topic><topic>Blood Cells - metabolism</topic><topic>Chromatin</topic><topic>Cohort Studies</topic><topic>CpG Islands</topic><topic>Data mining</topic><topic>Data processing</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Enhancers</topic><topic>Enrichment</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Ontology</topic><topic>Genes</topic><topic>Genetic transcription</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Humans</topic><topic>Insulators</topic><topic>Male</topic><topic>Methylation</topic><topic>MicroRNAs</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Promoters</topic><topic>Regulatory sequences</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Studies</topic><topic>Transcriptional regulation</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kennedy, Elizabeth M</creatorcontrib><creatorcontrib>Goehring, George N</creatorcontrib><creatorcontrib>Nichols, Michael H</creatorcontrib><creatorcontrib>Robins, Chloe</creatorcontrib><creatorcontrib>Mehta, Divya</creatorcontrib><creatorcontrib>Klengel, Torsten</creatorcontrib><creatorcontrib>Eskin, Eleazar</creatorcontrib><creatorcontrib>Smith, Alicia K</creatorcontrib><creatorcontrib>Conneely, Karen N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>BMC genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kennedy, Elizabeth M</au><au>Goehring, George N</au><au>Nichols, Michael H</au><au>Robins, Chloe</au><au>Mehta, Divya</au><au>Klengel, Torsten</au><au>Eskin, Eleazar</au><au>Smith, Alicia K</au><au>Conneely, Karen N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells</atitle><jtitle>BMC genomics</jtitle><addtitle>BMC Genomics</addtitle><date>2018-06-19</date><risdate>2018</risdate><volume>19</volume><issue>1</issue><spage>476</spage><epage>476</epage><pages>476-476</pages><artnum>476</artnum><issn>1471-2164</issn><eissn>1471-2164</eissn><abstract>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.
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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>29914364</pmid><doi>10.1186/s12864-018-4842-3</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0074-2840</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adolescent Adult Aged Analysis Atherosclerosis Binding sites Biological effects Blood Blood cells Blood Cells - metabolism Chromatin Cohort Studies CpG Islands Data mining Data processing Deoxyribonucleic acid DNA DNA Methylation Enhancers Enrichment Epigenesis, Genetic Epigenetic inheritance Epigenetics Female Gene expression Gene Expression Profiling Gene Ontology Genes Genetic transcription Genomes Genomics Humans Insulators Male Methylation MicroRNAs Middle Aged miRNA Promoters Regulatory sequences Ribonucleic acid RNA Studies Transcriptional regulation Young Adult |
title | An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells |
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