Discovery and characterization of human exonic transcriptional regulatory elements
We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-09, Vol.7 (9), p.e46098-e46098 |
|---|---|
| Hauptverfasser: | , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e46098 |
|---|---|
| container_issue | 9 |
| container_start_page | e46098 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Khan, Arshad H Lin, Andy Smith, Desmond J |
| description | We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome. |
| doi_str_mv | 10.1371/journal.pone.0046098 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_plos_</sourceid><recordid>TN_cdi_plos_journals_1326547634</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_e7ddf6fd1694459392de2c899988137d</doaj_id><sourcerecordid>2943678781</sourcerecordid><originalsourceid>FETCH-LOGICAL-c526t-561fcca1bc2ae0391b37d57e2a9ce6f4eae54b7bd0e7dc9a75c1eaf36f45e5a33</originalsourceid><addsrcrecordid>eNptUltrFDEUHkSxtfoPRAd88WXX3GfyIpR6KxQE0edwJjmzO0smWZOZYv31Zt1pacWnHPJdzoWvql5Ssqa8oe92cU4B_HofA64JEYro9lF1SjVnK8UIf3yvPqme5bwjRPJWqafVCeOEaUHIafXtw5BtvMZ0U0Nwtd1CAjthGn7DNMRQx77eziOEGn_FMNh6ShCyTcP-gIKvE25mD1MsevQ4Ypjy8-pJDz7ji-U9q358-vj94svq6uvny4vzq5WVTE0rqWhvLdDOMkDCNe1442SDDLRF1QsElKJrOkewcVZDIy1F6HmBJErg_Kx6ffTd-5jNco5sKGdKikZxURiXR4aLsDP7NIyQbkyEwfz9iGljIE2D9WhKD9er3lGlhZCaa-aQ2VZr3bbl3K54vV-6zd2IzpZNE_gHpg-RMGzNJl4bLqTgXBaDt4tBij9nzJMZy-nRewgY5zI3aZkgZXRdqG_-of5_O3Fk2RRzTtjfDUOJOUTkVmUOETFLRIrs1f1F7kS3meB_AI1nvKY</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1326547634</pqid></control><display><type>article</type><title>Discovery and characterization of human exonic transcriptional regulatory elements</title><source>MEDLINE</source><source>Public Library of Science</source><source>DOAJ Directory of Open Access Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Khan, Arshad H ; Lin, Andy ; Smith, Desmond J</creator><creatorcontrib>Khan, Arshad H ; Lin, Andy ; Smith, Desmond J</creatorcontrib><description>We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0046098</identifier><identifier>PMID: 23029400</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3' Untranslated Regions ; Binding Sites ; Biology ; Cell Line ; Chromatin ; Chromatin - genetics ; Chromatin - metabolism ; Cloning ; Cloning vectors ; Deoxyribonuclease I - metabolism ; Deoxyribonucleic acid ; DNA ; DNA, Complementary - genetics ; Enhancers ; Expression vectors ; Gene expression ; Gene sequencing ; Genome, Human ; Genomes ; Genomics ; Hepatocytes ; Histones - genetics ; Histones - metabolism ; Humans ; Liver ; Pharmacology ; Proteins ; Regulatory Elements, Transcriptional ; Regulatory sequences ; RNA polymerase ; Rodents ; Silencers ; Transcription factors ; Transcription Factors - metabolism ; Tubulin ; Tubulin - genetics</subject><ispartof>PloS one, 2012-09, Vol.7 (9), p.e46098-e46098</ispartof><rights>Khan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Khan et al 2012 Khan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-561fcca1bc2ae0391b37d57e2a9ce6f4eae54b7bd0e7dc9a75c1eaf36f45e5a33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454335/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3454335/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23029400$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, Arshad H</creatorcontrib><creatorcontrib>Lin, Andy</creatorcontrib><creatorcontrib>Smith, Desmond J</creatorcontrib><title>Discovery and characterization of human exonic transcriptional regulatory elements</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome.</description><subject>3' Untranslated Regions</subject><subject>Binding Sites</subject><subject>Biology</subject><subject>Cell Line</subject><subject>Chromatin</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Cloning</subject><subject>Cloning vectors</subject><subject>Deoxyribonuclease I - metabolism</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA, Complementary - genetics</subject><subject>Enhancers</subject><subject>Expression vectors</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genome, Human</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Hepatocytes</subject><subject>Histones - genetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Liver</subject><subject>Pharmacology</subject><subject>Proteins</subject><subject>Regulatory Elements, Transcriptional</subject><subject>Regulatory sequences</subject><subject>RNA polymerase</subject><subject>Rodents</subject><subject>Silencers</subject><subject>Transcription factors</subject><subject>Transcription Factors - metabolism</subject><subject>Tubulin</subject><subject>Tubulin - genetics</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptUltrFDEUHkSxtfoPRAd88WXX3GfyIpR6KxQE0edwJjmzO0smWZOZYv31Zt1pacWnHPJdzoWvql5Ssqa8oe92cU4B_HofA64JEYro9lF1SjVnK8UIf3yvPqme5bwjRPJWqafVCeOEaUHIafXtw5BtvMZ0U0Nwtd1CAjthGn7DNMRQx77eziOEGn_FMNh6ShCyTcP-gIKvE25mD1MsevQ4Ypjy8-pJDz7ji-U9q358-vj94svq6uvny4vzq5WVTE0rqWhvLdDOMkDCNe1442SDDLRF1QsElKJrOkewcVZDIy1F6HmBJErg_Kx6ffTd-5jNco5sKGdKikZxURiXR4aLsDP7NIyQbkyEwfz9iGljIE2D9WhKD9er3lGlhZCaa-aQ2VZr3bbl3K54vV-6zd2IzpZNE_gHpg-RMGzNJl4bLqTgXBaDt4tBij9nzJMZy-nRewgY5zI3aZkgZXRdqG_-of5_O3Fk2RRzTtjfDUOJOUTkVmUOETFLRIrs1f1F7kS3meB_AI1nvKY</recordid><startdate>20120924</startdate><enddate>20120924</enddate><creator>Khan, Arshad H</creator><creator>Lin, Andy</creator><creator>Smith, Desmond J</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120924</creationdate><title>Discovery and characterization of human exonic transcriptional regulatory elements</title><author>Khan, Arshad H ; Lin, Andy ; Smith, Desmond J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-561fcca1bc2ae0391b37d57e2a9ce6f4eae54b7bd0e7dc9a75c1eaf36f45e5a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>3' Untranslated Regions</topic><topic>Binding Sites</topic><topic>Biology</topic><topic>Cell Line</topic><topic>Chromatin</topic><topic>Chromatin - genetics</topic><topic>Chromatin - metabolism</topic><topic>Cloning</topic><topic>Cloning vectors</topic><topic>Deoxyribonuclease I - metabolism</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA, Complementary - genetics</topic><topic>Enhancers</topic><topic>Expression vectors</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genome, Human</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Hepatocytes</topic><topic>Histones - genetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Liver</topic><topic>Pharmacology</topic><topic>Proteins</topic><topic>Regulatory Elements, Transcriptional</topic><topic>Regulatory sequences</topic><topic>RNA polymerase</topic><topic>Rodents</topic><topic>Silencers</topic><topic>Transcription factors</topic><topic>Transcription Factors - metabolism</topic><topic>Tubulin</topic><topic>Tubulin - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, Arshad H</creatorcontrib><creatorcontrib>Lin, Andy</creatorcontrib><creatorcontrib>Smith, Desmond J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central</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>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</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>Engineering collection</collection><collection>Environmental Science Collection</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>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, Arshad H</au><au>Lin, Andy</au><au>Smith, Desmond J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery and characterization of human exonic transcriptional regulatory elements</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-09-24</date><risdate>2012</risdate><volume>7</volume><issue>9</issue><spage>e46098</spage><epage>e46098</epage><pages>e46098-e46098</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23029400</pmid><doi>10.1371/journal.pone.0046098</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-09, Vol.7 (9), p.e46098-e46098 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1326547634 |
| source | MEDLINE; Public Library of Science; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | 3' Untranslated Regions Binding Sites Biology Cell Line Chromatin Chromatin - genetics Chromatin - metabolism Cloning Cloning vectors Deoxyribonuclease I - metabolism Deoxyribonucleic acid DNA DNA, Complementary - genetics Enhancers Expression vectors Gene expression Gene sequencing Genome, Human Genomes Genomics Hepatocytes Histones - genetics Histones - metabolism Humans Liver Pharmacology Proteins Regulatory Elements, Transcriptional Regulatory sequences RNA polymerase Rodents Silencers Transcription factors Transcription Factors - metabolism Tubulin Tubulin - genetics |
| title | Discovery and characterization of human exonic transcriptional regulatory elements |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T17%3A49%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Discovery%20and%20characterization%20of%20human%20exonic%20transcriptional%20regulatory%20elements&rft.jtitle=PloS%20one&rft.au=Khan,%20Arshad%20H&rft.date=2012-09-24&rft.volume=7&rft.issue=9&rft.spage=e46098&rft.epage=e46098&rft.pages=e46098-e46098&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0046098&rft_dat=%3Cproquest_plos_%3E2943678781%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326547634&rft_id=info:pmid/23029400&rft_doaj_id=oai_doaj_org_article_e7ddf6fd1694459392de2c899988137d&rfr_iscdi=true |