Early Growth Response 1 (Egr1) Regulates Cholesterol Biosynthetic Gene Expression
The early growth response (EGR) family of transcription factors has been implicated in control of lipid biosynthetic genes. Egr1 is induced by insulin both in vitro and in vivo and is the most highly expressed family member in liver. In this study, we investigated whether Egr1 regulates cholesterol...
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| Veröffentlicht in: | The Journal of biological chemistry 2011-08, Vol.286 (34), p.29501-29510 |
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| creator | Gokey, Nolan G. Lopez-Anido, Camila Gillian-Daniel, Anne Lynn Svaren, John |
| description | The early growth response (EGR) family of transcription factors has been implicated in control of lipid biosynthetic genes. Egr1 is induced by insulin both in vitro and in vivo and is the most highly expressed family member in liver. In this study, we investigated whether Egr1 regulates cholesterol biosynthetic genes in liver. Using an insulin-sensitive liver cell line, we show that localization of Egr1 to cholesterol biosynthetic genes is induced by insulin treatment and that this localization precedes the induction of the genes. Reduction in Egr1 expression using targeted siRNA blunted the insulin-dependent induction of cholesterol genes. A similar reduction in squalene epoxidase expression was also observed in Egr1 null mice. In addition, application of chromatin immunoprecipitation (ChIP) samples to tiled gene microarrays revealed localization of Egr1 in promoter regions of many cholesterol gene loci. In vivo ChIP assays using liver tissue show that Egr1 localization to several cholesterol biosynthetic gene promoters is induced by feeding. Finally, analysis of plasma cholesterol in Egr1−/− mice indicated a significant decrease in serum cholesterol when compared with wild-type mice. Together these data point to Egr1 as a modulator of the cholesterol biosynthetic gene family in liver. |
| doi_str_mv | 10.1074/jbc.M111.263509 |
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Egr1 is induced by insulin both in vitro and in vivo and is the most highly expressed family member in liver. In this study, we investigated whether Egr1 regulates cholesterol biosynthetic genes in liver. Using an insulin-sensitive liver cell line, we show that localization of Egr1 to cholesterol biosynthetic genes is induced by insulin treatment and that this localization precedes the induction of the genes. Reduction in Egr1 expression using targeted siRNA blunted the insulin-dependent induction of cholesterol genes. A similar reduction in squalene epoxidase expression was also observed in Egr1 null mice. In addition, application of chromatin immunoprecipitation (ChIP) samples to tiled gene microarrays revealed localization of Egr1 in promoter regions of many cholesterol gene loci. In vivo ChIP assays using liver tissue show that Egr1 localization to several cholesterol biosynthetic gene promoters is induced by feeding. Finally, analysis of plasma cholesterol in Egr1−/− mice indicated a significant decrease in serum cholesterol when compared with wild-type mice. Together these data point to Egr1 as a modulator of the cholesterol biosynthetic gene family in liver.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M111.263509</identifier><identifier>PMID: 21712389</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cholesterol ; Cholesterol - biosynthesis ; Cholesterol - genetics ; Cholesterol Regulation ; Chromatin Immunoprecipitation (ChIP) ; Early Growth Response Protein 1 - genetics ; Early Growth Response Protein 1 - metabolism ; Gene Expression ; Gene Expression Regulation - drug effects ; Gene Expression Regulation - physiology ; Gene Regulation ; Hepatocyte ; High Density Lipoprotein (HDL) ; Humans ; Hypoglycemic Agents - pharmacology ; Insulin ; Insulin - pharmacology ; Lipid Synthesis ; Liver - metabolism ; Mice ; Mice, Mutant Strains ; Promoter Regions, Genetic - physiology ; Rats ; Transcription Factors</subject><ispartof>The Journal of biological chemistry, 2011-08, Vol.286 (34), p.29501-29510</ispartof><rights>2011 © 2011 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2011 by The American Society for Biochemistry and Molecular Biology, Inc. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-27c6d9b92f37424d470f3d21b9508e50655a5f0846edb706709b61ad784a49bf3</citedby><cites>FETCH-LOGICAL-c442t-27c6d9b92f37424d470f3d21b9508e50655a5f0846edb706709b61ad784a49bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190990/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3190990/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,27911,27912,53778,53780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21712389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gokey, Nolan G.</creatorcontrib><creatorcontrib>Lopez-Anido, Camila</creatorcontrib><creatorcontrib>Gillian-Daniel, Anne Lynn</creatorcontrib><creatorcontrib>Svaren, John</creatorcontrib><title>Early Growth Response 1 (Egr1) Regulates Cholesterol Biosynthetic Gene Expression</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The early growth response (EGR) family of transcription factors has been implicated in control of lipid biosynthetic genes. Egr1 is induced by insulin both in vitro and in vivo and is the most highly expressed family member in liver. In this study, we investigated whether Egr1 regulates cholesterol biosynthetic genes in liver. Using an insulin-sensitive liver cell line, we show that localization of Egr1 to cholesterol biosynthetic genes is induced by insulin treatment and that this localization precedes the induction of the genes. Reduction in Egr1 expression using targeted siRNA blunted the insulin-dependent induction of cholesterol genes. A similar reduction in squalene epoxidase expression was also observed in Egr1 null mice. In addition, application of chromatin immunoprecipitation (ChIP) samples to tiled gene microarrays revealed localization of Egr1 in promoter regions of many cholesterol gene loci. In vivo ChIP assays using liver tissue show that Egr1 localization to several cholesterol biosynthetic gene promoters is induced by feeding. Finally, analysis of plasma cholesterol in Egr1−/− mice indicated a significant decrease in serum cholesterol when compared with wild-type mice. Together these data point to Egr1 as a modulator of the cholesterol biosynthetic gene family in liver.</description><subject>Animals</subject><subject>Cholesterol</subject><subject>Cholesterol - biosynthesis</subject><subject>Cholesterol - genetics</subject><subject>Cholesterol Regulation</subject><subject>Chromatin Immunoprecipitation (ChIP)</subject><subject>Early Growth Response Protein 1 - genetics</subject><subject>Early Growth Response Protein 1 - metabolism</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Expression Regulation - physiology</subject><subject>Gene Regulation</subject><subject>Hepatocyte</subject><subject>High Density Lipoprotein (HDL)</subject><subject>Humans</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Insulin - pharmacology</subject><subject>Lipid Synthesis</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Promoter Regions, Genetic - physiology</subject><subject>Rats</subject><subject>Transcription Factors</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM1LAzEQxYMotlbP3mSPetg2k81-5CJoqVWoiKLgLWSzs23KdlOSbbX_vVuqRQ_OZWDmvTfMj5BzoH2gKR_Mc91_BIA-S6KYigPSBZpFYRTD-yHpUsogFCzOOuTE-zltiws4Jh0GKbAoE13yPFKu2gRjZz-aWfCCfmlrjwEEl6Opg6t2Ml1VqkEfDGe2Qt-gs1Vwa6zf1M0MG6ODMdYYjD6XDr03tj4lR6WqPJ599x55uxu9Du_DydP4YXgzCTXnrAlZqpNC5IKVUcoZL3hKy6hgkIuYZhjTJI5VXNKMJ1jkKU1SKvIEVJFmXHGRl1GPXO9yl6t8gYXGunGqkktnFsptpFVG_t3UZiandi0jEFQI2gYMdgHaWe8dlnsvULmlK1u6cktX7ui2jovfJ_f6H5ytQOwE2D6-Nuik1wZrjYVxqBtZWPNv-BfJxomw</recordid><startdate>20110826</startdate><enddate>20110826</enddate><creator>Gokey, Nolan G.</creator><creator>Lopez-Anido, Camila</creator><creator>Gillian-Daniel, Anne Lynn</creator><creator>Svaren, John</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</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>5PM</scope></search><sort><creationdate>20110826</creationdate><title>Early Growth Response 1 (Egr1) Regulates Cholesterol Biosynthetic Gene Expression</title><author>Gokey, Nolan G. ; Lopez-Anido, Camila ; Gillian-Daniel, Anne Lynn ; Svaren, John</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-27c6d9b92f37424d470f3d21b9508e50655a5f0846edb706709b61ad784a49bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Cholesterol</topic><topic>Cholesterol - biosynthesis</topic><topic>Cholesterol - genetics</topic><topic>Cholesterol Regulation</topic><topic>Chromatin Immunoprecipitation (ChIP)</topic><topic>Early Growth Response Protein 1 - genetics</topic><topic>Early Growth Response Protein 1 - metabolism</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Expression Regulation - physiology</topic><topic>Gene Regulation</topic><topic>Hepatocyte</topic><topic>High Density Lipoprotein (HDL)</topic><topic>Humans</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Insulin - pharmacology</topic><topic>Lipid Synthesis</topic><topic>Liver - metabolism</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Promoter Regions, Genetic - physiology</topic><topic>Rats</topic><topic>Transcription Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gokey, Nolan G.</creatorcontrib><creatorcontrib>Lopez-Anido, Camila</creatorcontrib><creatorcontrib>Gillian-Daniel, Anne Lynn</creatorcontrib><creatorcontrib>Svaren, John</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gokey, Nolan G.</au><au>Lopez-Anido, Camila</au><au>Gillian-Daniel, Anne Lynn</au><au>Svaren, John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early Growth Response 1 (Egr1) Regulates Cholesterol Biosynthetic Gene Expression</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2011-08-26</date><risdate>2011</risdate><volume>286</volume><issue>34</issue><spage>29501</spage><epage>29510</epage><pages>29501-29510</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>The early growth response (EGR) family of transcription factors has been implicated in control of lipid biosynthetic genes. Egr1 is induced by insulin both in vitro and in vivo and is the most highly expressed family member in liver. In this study, we investigated whether Egr1 regulates cholesterol biosynthetic genes in liver. Using an insulin-sensitive liver cell line, we show that localization of Egr1 to cholesterol biosynthetic genes is induced by insulin treatment and that this localization precedes the induction of the genes. Reduction in Egr1 expression using targeted siRNA blunted the insulin-dependent induction of cholesterol genes. A similar reduction in squalene epoxidase expression was also observed in Egr1 null mice. In addition, application of chromatin immunoprecipitation (ChIP) samples to tiled gene microarrays revealed localization of Egr1 in promoter regions of many cholesterol gene loci. In vivo ChIP assays using liver tissue show that Egr1 localization to several cholesterol biosynthetic gene promoters is induced by feeding. Finally, analysis of plasma cholesterol in Egr1−/− mice indicated a significant decrease in serum cholesterol when compared with wild-type mice. Together these data point to Egr1 as a modulator of the cholesterol biosynthetic gene family in liver.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21712389</pmid><doi>10.1074/jbc.M111.263509</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Cholesterol Cholesterol - biosynthesis Cholesterol - genetics Cholesterol Regulation Chromatin Immunoprecipitation (ChIP) Early Growth Response Protein 1 - genetics Early Growth Response Protein 1 - metabolism Gene Expression Gene Expression Regulation - drug effects Gene Expression Regulation - physiology Gene Regulation Hepatocyte High Density Lipoprotein (HDL) Humans Hypoglycemic Agents - pharmacology Insulin Insulin - pharmacology Lipid Synthesis Liver - metabolism Mice Mice, Mutant Strains Promoter Regions, Genetic - physiology Rats Transcription Factors |
| title | Early Growth Response 1 (Egr1) Regulates Cholesterol Biosynthetic Gene Expression |
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