Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells
OBJECTIVE—MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription f...
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| Veröffentlicht in: | Arteriosclerosis, thrombosis, and vascular biology thrombosis, and vascular biology, 2010-10, Vol.30 (10), p.1990-1997 |
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| container_end_page | 1997 |
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| container_issue | 10 |
| container_start_page | 1990 |
| container_title | Arteriosclerosis, thrombosis, and vascular biology |
| container_volume | 30 |
| creator | Harris, Tamia A Yamakuchi, Munekazu Kondo, Maiko Oettgen, Peter Lowenstein, Charles J |
| description | OBJECTIVE—MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression.
METHODS AND RESULTS—A genomic region between −71 and −100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.
CONCLUSION—Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects. |
| doi_str_mv | 10.1161/ATVBAHA.110.211706 |
| format | Article |
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METHODS AND RESULTS—A genomic region between −71 and −100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.
CONCLUSION—Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects.</description><identifier>ISSN: 1079-5642</identifier><identifier>EISSN: 1524-4636</identifier><identifier>DOI: 10.1161/ATVBAHA.110.211706</identifier><identifier>PMID: 20671229</identifier><identifier>CODEN: ATVBFA</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>Animals ; Atherosclerosis (general aspects, experimental research) ; Base Sequence ; Binding Sites - genetics ; Biological and medical sciences ; Blood and lymphatic vessels ; Blood vessels and receptors ; Cardiology. Vascular system ; Cells, Cultured ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; DNA Primers - genetics ; Endothelial Cells - metabolism ; Endothelial Growth Factors - genetics ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Humans ; Luciferases - genetics ; Medical sciences ; Mice ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Molecular Sequence Data ; Promoter Regions, Genetic ; Proteins - genetics ; Proto-Oncogene Protein c-ets-1 - metabolism ; Proto-Oncogene Protein c-ets-2 - metabolism ; Sequence Deletion ; Signal Transduction ; Transcriptional Activation ; Vertebrates: cardiovascular system</subject><ispartof>Arteriosclerosis, thrombosis, and vascular biology, 2010-10, Vol.30 (10), p.1990-1997</ispartof><rights>2010 American Heart Association, Inc.</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5369-59bc0c34dea7e058990057c0f68ec4de6ac286b5741b5b5e2cf3d5a9ddfa563e3</citedby><cites>FETCH-LOGICAL-c5369-59bc0c34dea7e058990057c0f68ec4de6ac286b5741b5b5e2cf3d5a9ddfa563e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23234855$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20671229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Harris, Tamia A</creatorcontrib><creatorcontrib>Yamakuchi, Munekazu</creatorcontrib><creatorcontrib>Kondo, Maiko</creatorcontrib><creatorcontrib>Oettgen, Peter</creatorcontrib><creatorcontrib>Lowenstein, Charles J</creatorcontrib><title>Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells</title><title>Arteriosclerosis, thrombosis, and vascular biology</title><addtitle>Arterioscler Thromb Vasc Biol</addtitle><description>OBJECTIVE—MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression.
METHODS AND RESULTS—A genomic region between −71 and −100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.
CONCLUSION—Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects.</description><subject>Animals</subject><subject>Atherosclerosis (general aspects, experimental research)</subject><subject>Base Sequence</subject><subject>Binding Sites - genetics</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Blood vessels and receptors</subject><subject>Cardiology. Vascular system</subject><subject>Cells, Cultured</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>DNA Primers - genetics</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Growth Factors - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Luciferases - genetics</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Molecular Sequence Data</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins - genetics</subject><subject>Proto-Oncogene Protein c-ets-1 - metabolism</subject><subject>Proto-Oncogene Protein c-ets-2 - metabolism</subject><subject>Sequence Deletion</subject><subject>Signal Transduction</subject><subject>Transcriptional Activation</subject><subject>Vertebrates: cardiovascular system</subject><issn>1079-5642</issn><issn>1524-4636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkNFOwyAUhonROJ2-gBeGGy-ZByi0vaxLdSZTk2V621BKXZW1C3SZvr0snQohnEO-n5x8CF1RmFAq6W22fLvLZlloYMIojUEeoTMqWEQiyeVxqCFOiZARG6Fz7z8AIGIMTtGIgYwpY-kZmue9JxSrtsL7iuGFed9a1RvcrwzOvzbOeN90Le5q_NRo1y2eM0KZxE2L87bqAmUbZfHUWOsv0EmtrDeXh3uMXu_z5XRG5i8Pj9NsTrTgMkyUlho0jyqjYgMiSVMAEWuoZWJ0eJVKs0SWIo5oKUphmK55JVRaVbUSkhs-Rmz4N8zjvTN1sXHNWrnvgkKxV1Mc1IQGikFNCF0Poc22XJvqL_LrIgA3B0B5rWztVKsb_89xxqNEiMBFA7frbG-c_7TbnXHFyijbr4q9ZC5BEAY07LBIODTlP8NwedY</recordid><startdate>201010</startdate><enddate>201010</enddate><creator>Harris, Tamia A</creator><creator>Yamakuchi, Munekazu</creator><creator>Kondo, Maiko</creator><creator>Oettgen, Peter</creator><creator>Lowenstein, Charles J</creator><general>American Heart Association, Inc</general><general>Lippincott Williams & Wilkins</general><scope>IQODW</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></search><sort><creationdate>201010</creationdate><title>Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells</title><author>Harris, Tamia A ; Yamakuchi, Munekazu ; Kondo, Maiko ; Oettgen, Peter ; Lowenstein, Charles J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5369-59bc0c34dea7e058990057c0f68ec4de6ac286b5741b5b5e2cf3d5a9ddfa563e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Atherosclerosis (general aspects, experimental research)</topic><topic>Base Sequence</topic><topic>Binding Sites - genetics</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Blood vessels and receptors</topic><topic>Cardiology. Vascular system</topic><topic>Cells, Cultured</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>DNA Primers - genetics</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelial Growth Factors - genetics</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Luciferases - genetics</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Molecular Sequence Data</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins - genetics</topic><topic>Proto-Oncogene Protein c-ets-1 - metabolism</topic><topic>Proto-Oncogene Protein c-ets-2 - metabolism</topic><topic>Sequence Deletion</topic><topic>Signal Transduction</topic><topic>Transcriptional Activation</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Harris, Tamia A</creatorcontrib><creatorcontrib>Yamakuchi, Munekazu</creatorcontrib><creatorcontrib>Kondo, Maiko</creatorcontrib><creatorcontrib>Oettgen, Peter</creatorcontrib><creatorcontrib>Lowenstein, Charles J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Harris, Tamia A</au><au>Yamakuchi, Munekazu</au><au>Kondo, Maiko</au><au>Oettgen, Peter</au><au>Lowenstein, Charles J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells</atitle><jtitle>Arteriosclerosis, thrombosis, and vascular biology</jtitle><addtitle>Arterioscler Thromb Vasc Biol</addtitle><date>2010-10</date><risdate>2010</risdate><volume>30</volume><issue>10</issue><spage>1990</spage><epage>1997</epage><pages>1990-1997</pages><issn>1079-5642</issn><eissn>1524-4636</eissn><coden>ATVBFA</coden><abstract>OBJECTIVE—MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression.
METHODS AND RESULTS—A genomic region between −71 and −100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene.
CONCLUSION—Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects.</abstract><cop>Philadelphia, PA</cop><pub>American Heart Association, Inc</pub><pmid>20671229</pmid><doi>10.1161/ATVBAHA.110.211706</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Arteriosclerosis, thrombosis, and vascular biology, 2010-10, Vol.30 (10), p.1990-1997 |
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| subjects | Animals Atherosclerosis (general aspects, experimental research) Base Sequence Binding Sites - genetics Biological and medical sciences Blood and lymphatic vessels Blood vessels and receptors Cardiology. Vascular system Cells, Cultured Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous DNA Primers - genetics Endothelial Cells - metabolism Endothelial Growth Factors - genetics Fundamental and applied biological sciences. Psychology Gene Expression Profiling Humans Luciferases - genetics Medical sciences Mice MicroRNAs - genetics MicroRNAs - metabolism Molecular Sequence Data Promoter Regions, Genetic Proteins - genetics Proto-Oncogene Protein c-ets-1 - metabolism Proto-Oncogene Protein c-ets-2 - metabolism Sequence Deletion Signal Transduction Transcriptional Activation Vertebrates: cardiovascular system |
| title | Ets-1 and Ets-2 Regulate the Expression of MicroRNA-126 in Endothelial Cells |
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