TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements
TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2012-04, Vol.109 (16), p.6030-6035 |
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| creator | Tan, Adelene Y Riley, Todd R Coady, Tristan Bussemaker, Harmen J Manley, James L |
| description | TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS. Among these genes, we detected a number that correlate with previously known functions of TLS, and confirmed TLS occupancy at several of them by ChIP. We also detected changes in mRNA levels of these target genes in cells where TLS levels were altered, indicative of both activation and repression. Next, we used data from the microarray and computational methods to determine whether specific sequences were enriched in DNA fragments bound by TLS. This analysis suggested the existence of TLS response elements, and we show that purified TLS indeed binds these sequences with specificity in vitro. Remarkably, however, TLS binds only single-strand versions of the sequences. Taken together, our results indicate that TLS regulates expression of specific target genes, likely via recognition of specific single-stranded DNA sequences located within their promoter regions. |
| doi_str_mv | 10.1073/pnas.1203028109 |
| format | Article |
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However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS. Among these genes, we detected a number that correlate with previously known functions of TLS, and confirmed TLS occupancy at several of them by ChIP. We also detected changes in mRNA levels of these target genes in cells where TLS levels were altered, indicative of both activation and repression. Next, we used data from the microarray and computational methods to determine whether specific sequences were enriched in DNA fragments bound by TLS. This analysis suggested the existence of TLS response elements, and we show that purified TLS indeed binds these sequences with specificity in vitro. Remarkably, however, TLS binds only single-strand versions of the sequences. Taken together, our results indicate that TLS regulates expression of specific target genes, likely via recognition of specific single-stranded DNA sequences located within their promoter regions.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1203028109</identifier><identifier>PMID: 22460799</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Amyotrophic lateral sclerosis ; Base Sequence ; Binding, Competitive ; bioinformatics ; Biological Sciences ; Blotting, Western ; Cancer ; Cell Line, Tumor ; Cell lines ; Cells ; Chromatin Immunoprecipitation ; Computational neuroscience ; Data processing ; Deoxyribonucleic acid ; DNA ; DNA microarrays ; DNA, Single-Stranded ; DNA, Single-Stranded - genetics ; FUS protein ; Gene Expression Profiling ; Gene expression regulation ; Gene Expression Regulation, Neoplastic ; Genes ; genetics ; Heterogeneous nuclear ribonucleoproteins ; Humans ; Messenger RNA ; metabolism ; microarray technology ; mRNA processing ; Neurological diseases ; Nucleotide sequence ; Oligonucleotide Array Sequence Analysis ; Promoter regions ; Promoter Regions, Genetic ; Promoter Regions, Genetic - genetics ; Promoters ; Protein Binding ; Protein Interaction Domains and Motifs ; Protein Interaction Domains and Motifs - genetics ; Regulatory sequences ; response elements ; Response Elements - genetics ; RNA ; RNA-Binding Protein FUS ; RNA-Binding Protein FUS - genetics ; RNA-Binding Protein FUS - metabolism ; Sarcoma ; single-stranded DNA ; Transcription ; transcription (genetics) ; Transcriptional regulatory elements</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2012-04, Vol.109 (16), p.6030-6035</ispartof><rights>copyright © 1993-2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Apr 17, 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-92e185d46be30648fe6956ab1b59be66e29c720be0fd33fe3089d9d45824e7d3</citedby><cites>FETCH-LOGICAL-c623t-92e185d46be30648fe6956ab1b59be66e29c720be0fd33fe3089d9d45824e7d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/109/16.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/41588468$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/41588468$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22460799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tan, Adelene Y</creatorcontrib><creatorcontrib>Riley, Todd R</creatorcontrib><creatorcontrib>Coady, Tristan</creatorcontrib><creatorcontrib>Bussemaker, Harmen J</creatorcontrib><creatorcontrib>Manley, James L</creatorcontrib><title>TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS. Among these genes, we detected a number that correlate with previously known functions of TLS, and confirmed TLS occupancy at several of them by ChIP. We also detected changes in mRNA levels of these target genes in cells where TLS levels were altered, indicative of both activation and repression. Next, we used data from the microarray and computational methods to determine whether specific sequences were enriched in DNA fragments bound by TLS. This analysis suggested the existence of TLS response elements, and we show that purified TLS indeed binds these sequences with specificity in vitro. Remarkably, however, TLS binds only single-strand versions of the sequences. Taken together, our results indicate that TLS regulates expression of specific target genes, likely via recognition of specific single-stranded DNA sequences located within their promoter regions.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Base Sequence</subject><subject>Binding, Competitive</subject><subject>bioinformatics</subject><subject>Biological Sciences</subject><subject>Blotting, Western</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cells</subject><subject>Chromatin Immunoprecipitation</subject><subject>Computational neuroscience</subject><subject>Data processing</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA microarrays</subject><subject>DNA, Single-Stranded</subject><subject>DNA, Single-Stranded - genetics</subject><subject>FUS protein</subject><subject>Gene Expression Profiling</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes</subject><subject>genetics</subject><subject>Heterogeneous nuclear ribonucleoproteins</subject><subject>Humans</subject><subject>Messenger RNA</subject><subject>metabolism</subject><subject>microarray technology</subject><subject>mRNA processing</subject><subject>Neurological diseases</subject><subject>Nucleotide sequence</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Promoter regions</subject><subject>Promoter Regions, Genetic</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Promoters</subject><subject>Protein Binding</subject><subject>Protein Interaction Domains and Motifs</subject><subject>Protein Interaction Domains and Motifs - genetics</subject><subject>Regulatory sequences</subject><subject>response elements</subject><subject>Response Elements - genetics</subject><subject>RNA</subject><subject>RNA-Binding Protein FUS</subject><subject>RNA-Binding Protein FUS - genetics</subject><subject>RNA-Binding Protein FUS - metabolism</subject><subject>Sarcoma</subject><subject>single-stranded DNA</subject><subject>Transcription</subject><subject>transcription (genetics)</subject><subject>Transcriptional regulatory elements</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2P0zAQhiMEYsvCmRMQictyyHb8Ede-IK0WFpAqOLR7tpxkElyldtZOVuLOD8elpQUucLGlmWfe8YzfLHtO4JLAgs0HZ-IlocCASgLqQTZLJykEV_AwmwHQRSE55WfZkxg3AKBKCY-zM0q5gIVSs-z7erma39yu8osxGBd7X5sRm9y6vLeDjybUfmvm7RT3wUPgTR6wm_qExnw0ocMx79Bh_lOjDnYYrXf5vTV5tK7rsYi7TJM03n2-SrVx8C5ijj1u0Y3xafaoNX3EZ4f7PFvfvF9ffyyWXz58ur5aFrWgbCwURSLLhosKGQguWxSqFKYiVakqFAKpqhcUKoS2YaxNkFSNangpKcdFw86zt3vZYaq22NSpdTC9HoLdmvBNe2P1nxlnv-rO32vGOEkNk8DFQSD4uwnjqLc21tj3xqGfoiZCsJIywem_UaAgS07k_6DpGxXnUCb09V_oxk_BpZ3tKCm4kBISNd9TdfAxBmyPIxLQO9vonW30yTap4uXvmznyv3ySgFcHYFd5klNpZi2STiJe7IlNHH04IpyUUqZnnRRa47Xpgo36dkWBcAAihZKS_QCACtw5</recordid><startdate>20120417</startdate><enddate>20120417</enddate><creator>Tan, Adelene Y</creator><creator>Riley, Todd R</creator><creator>Coady, Tristan</creator><creator>Bussemaker, Harmen J</creator><creator>Manley, James L</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20120417</creationdate><title>TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements</title><author>Tan, Adelene Y ; Riley, Todd R ; Coady, Tristan ; Bussemaker, Harmen J ; Manley, James L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c623t-92e185d46be30648fe6956ab1b59be66e29c720be0fd33fe3089d9d45824e7d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Amyotrophic lateral sclerosis</topic><topic>Base Sequence</topic><topic>Binding, Competitive</topic><topic>bioinformatics</topic><topic>Biological Sciences</topic><topic>Blotting, Western</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cells</topic><topic>Chromatin Immunoprecipitation</topic><topic>Computational neuroscience</topic><topic>Data processing</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA microarrays</topic><topic>DNA, Single-Stranded</topic><topic>DNA, Single-Stranded - genetics</topic><topic>FUS protein</topic><topic>Gene Expression Profiling</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>genetics</topic><topic>Heterogeneous nuclear ribonucleoproteins</topic><topic>Humans</topic><topic>Messenger RNA</topic><topic>metabolism</topic><topic>microarray technology</topic><topic>mRNA processing</topic><topic>Neurological diseases</topic><topic>Nucleotide sequence</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Promoter regions</topic><topic>Promoter Regions, Genetic</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Promoters</topic><topic>Protein Binding</topic><topic>Protein Interaction Domains and Motifs</topic><topic>Protein Interaction Domains and Motifs - genetics</topic><topic>Regulatory sequences</topic><topic>response elements</topic><topic>Response Elements - genetics</topic><topic>RNA</topic><topic>RNA-Binding Protein FUS</topic><topic>RNA-Binding Protein FUS - genetics</topic><topic>RNA-Binding Protein FUS - metabolism</topic><topic>Sarcoma</topic><topic>single-stranded DNA</topic><topic>Transcription</topic><topic>transcription (genetics)</topic><topic>Transcriptional regulatory elements</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tan, Adelene Y</creatorcontrib><creatorcontrib>Riley, Todd R</creatorcontrib><creatorcontrib>Coady, Tristan</creatorcontrib><creatorcontrib>Bussemaker, Harmen J</creatorcontrib><creatorcontrib>Manley, James L</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tan, Adelene Y</au><au>Riley, Todd R</au><au>Coady, Tristan</au><au>Bussemaker, Harmen J</au><au>Manley, James L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2012-04-17</date><risdate>2012</risdate><volume>109</volume><issue>16</issue><spage>6030</spage><epage>6035</epage><pages>6030-6035</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>TLS/FUS (TLS) is a multifunctional protein implicated in a wide range of cellular processes, including transcription and mRNA processing, as well as in both cancer and neurological disease. However, little is currently known about TLS target genes and how they are recognized. Here, we used ChIP and promoter microarrays to identify genes potentially regulated by TLS. Among these genes, we detected a number that correlate with previously known functions of TLS, and confirmed TLS occupancy at several of them by ChIP. We also detected changes in mRNA levels of these target genes in cells where TLS levels were altered, indicative of both activation and repression. Next, we used data from the microarray and computational methods to determine whether specific sequences were enriched in DNA fragments bound by TLS. This analysis suggested the existence of TLS response elements, and we show that purified TLS indeed binds these sequences with specificity in vitro. Remarkably, however, TLS binds only single-strand versions of the sequences. Taken together, our results indicate that TLS regulates expression of specific target genes, likely via recognition of specific single-stranded DNA sequences located within their promoter regions.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22460799</pmid><doi>10.1073/pnas.1203028109</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| source | Jstor Complete Legacy; MEDLINE; PMC (PubMed Central); Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Amyotrophic lateral sclerosis Base Sequence Binding, Competitive bioinformatics Biological Sciences Blotting, Western Cancer Cell Line, Tumor Cell lines Cells Chromatin Immunoprecipitation Computational neuroscience Data processing Deoxyribonucleic acid DNA DNA microarrays DNA, Single-Stranded DNA, Single-Stranded - genetics FUS protein Gene Expression Profiling Gene expression regulation Gene Expression Regulation, Neoplastic Genes genetics Heterogeneous nuclear ribonucleoproteins Humans Messenger RNA metabolism microarray technology mRNA processing Neurological diseases Nucleotide sequence Oligonucleotide Array Sequence Analysis Promoter regions Promoter Regions, Genetic Promoter Regions, Genetic - genetics Promoters Protein Binding Protein Interaction Domains and Motifs Protein Interaction Domains and Motifs - genetics Regulatory sequences response elements Response Elements - genetics RNA RNA-Binding Protein FUS RNA-Binding Protein FUS - genetics RNA-Binding Protein FUS - metabolism Sarcoma single-stranded DNA Transcription transcription (genetics) Transcriptional regulatory elements |
| title | TLS/FUS (translocated in liposarcoma/fused in sarcoma) regulates target gene transcription via single-stranded DNA response elements |
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