The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development
The homeodomain protein Cux1 is highly expressed in the nephrogenic zone of the developing kidney where it functions to regulate cell proliferation. Here we show that Cux1 directly interacts with the co-repressor Grg4 (Groucho 4), a known effector of Notch signaling. Promoter reporter based lucifera...
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| Veröffentlicht in: | Gene 2009-06, Vol.439 (1), p.87-94 |
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| creator | Sharma, Madhulika Brantley, Jennifer G. Vassmer, Dianne Chaturvedi, Gaurav Baas, Jennifer Vanden Heuvel, Gregory B. |
| description | The homeodomain protein Cux1 is highly expressed in the nephrogenic zone of the developing kidney where it functions to regulate cell proliferation. Here we show that Cux1 directly interacts with the co-repressor Grg4 (Groucho 4), a known effector of Notch signaling. Promoter reporter based luciferase assays revealed enhanced repression of
p27
kip1
promoter activity by Cux1 in the presence of Grg4. Chromatin immunoprecipitation (ChIP) assays demonstrated the direct interaction of Cux1 with
p27
kip1
in newborn kidney tissue
in vivo. ChIP assays also identified interactions of Cux1, Grg4, HDAC1, and HDAC3 with
p27
kip1
at two separate sites in the
p27
kip1
promoter. DNAse1 footprinting experiments revealed that Cux1 binds to the
p27
kip1
promoter on the sequence containing two Sp1 sites and a CCAAT box ∼
500 bp from the transcriptional start site, and to an AT rich sequence ∼
1.5 kb from the transcriptional start site. Taken together, these results identify Grg4 as an interacting partner for Cux1 and suggest a mechanism of
p27
kip1
repression by Cux1 during kidney development. |
| doi_str_mv | 10.1016/j.gene.2009.03.014 |
| format | Article |
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p27
kip1
promoter activity by Cux1 in the presence of Grg4. Chromatin immunoprecipitation (ChIP) assays demonstrated the direct interaction of Cux1 with
p27
kip1
in newborn kidney tissue
in vivo. ChIP assays also identified interactions of Cux1, Grg4, HDAC1, and HDAC3 with
p27
kip1
at two separate sites in the
p27
kip1
promoter. DNAse1 footprinting experiments revealed that Cux1 binds to the
p27
kip1
promoter on the sequence containing two Sp1 sites and a CCAAT box ∼
500 bp from the transcriptional start site, and to an AT rich sequence ∼
1.5 kb from the transcriptional start site. Taken together, these results identify Grg4 as an interacting partner for Cux1 and suggest a mechanism of
p27
kip1
repression by Cux1 during kidney development.</description><identifier>ISSN: 0378-1119</identifier><identifier>EISSN: 1879-0038</identifier><identifier>DOI: 10.1016/j.gene.2009.03.014</identifier><identifier>PMID: 19332113</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Animals, Newborn ; Binding Sites ; CCAAT-Enhancer-Binding Proteins - genetics ; CCAAT-Enhancer-Binding Proteins - metabolism ; Cell Line ; Chromatin Immunoprecipitation ; Cyclin-Dependent Kinase Inhibitor p27 - genetics ; Cyclin-Dependent Kinase Inhibitor p27 - metabolism ; Gene Expression Regulation, Developmental ; Homeodomain Proteins - genetics ; Homeodomain Proteins - metabolism ; Humans ; Kidney - growth & development ; Kidney - metabolism ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; Promoter Regions, Genetic ; Protein Binding ; Repressor Proteins - genetics ; Repressor Proteins - metabolism</subject><ispartof>Gene, 2009-06, Vol.439 (1), p.87-94</ispartof><rights>2009 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S037811190900136X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19332113$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sharma, Madhulika</creatorcontrib><creatorcontrib>Brantley, Jennifer G.</creatorcontrib><creatorcontrib>Vassmer, Dianne</creatorcontrib><creatorcontrib>Chaturvedi, Gaurav</creatorcontrib><creatorcontrib>Baas, Jennifer</creatorcontrib><creatorcontrib>Vanden Heuvel, Gregory B.</creatorcontrib><title>The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development</title><title>Gene</title><addtitle>Gene</addtitle><description>The homeodomain protein Cux1 is highly expressed in the nephrogenic zone of the developing kidney where it functions to regulate cell proliferation. Here we show that Cux1 directly interacts with the co-repressor Grg4 (Groucho 4), a known effector of Notch signaling. Promoter reporter based luciferase assays revealed enhanced repression of
p27
kip1
promoter activity by Cux1 in the presence of Grg4. Chromatin immunoprecipitation (ChIP) assays demonstrated the direct interaction of Cux1 with
p27
kip1
in newborn kidney tissue
in vivo. ChIP assays also identified interactions of Cux1, Grg4, HDAC1, and HDAC3 with
p27
kip1
at two separate sites in the
p27
kip1
promoter. DNAse1 footprinting experiments revealed that Cux1 binds to the
p27
kip1
promoter on the sequence containing two Sp1 sites and a CCAAT box ∼
500 bp from the transcriptional start site, and to an AT rich sequence ∼
1.5 kb from the transcriptional start site. Taken together, these results identify Grg4 as an interacting partner for Cux1 and suggest a mechanism of
p27
kip1
repression by Cux1 during kidney development.</description><subject>Animals</subject><subject>Animals, Newborn</subject><subject>Binding Sites</subject><subject>CCAAT-Enhancer-Binding Proteins - genetics</subject><subject>CCAAT-Enhancer-Binding Proteins - metabolism</subject><subject>Cell Line</subject><subject>Chromatin Immunoprecipitation</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - genetics</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Kidney - growth & development</subject><subject>Kidney - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><issn>0378-1119</issn><issn>1879-0038</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kU1PwzAMhiMEgjH4AxxQTtxa7KRdG4kLmviSkLjAOeoSs2WsSUlaYP-ejg9fXunVY8v2y9gZQo6As8t1viRPuQBQOcgcsNhjE6wrlQHIep9NQFZ1hojqiB2ntIaxylIcsiNUUgpEOWHueUV8FVoKNrSN87yLoadR58MXcud7io3pE_90_YrfxWXB-8AjdZFS4p2o-JvrkNPXj-GC53aIzi9H23racksftAldS74_YQevzSbR6Z9O2cvtzfP8Pnt8unuYXz9mhFDJTCoJQtEMoBBgbGVIlaKAWuBCGRClgJKq2QJt05RFTaaSZEtDr_WupbEop-zid-54yftAqdetS4Y2m8ZTGJKeVUIqLOsRPP8Dh0VLVnfRtU3c6v_njMDVL0Djuh-Ook7GkTdkXSTTaxucRtC7LPRa77LQuyw0SD1mIb8BWlZ7-g</recordid><startdate>20090615</startdate><enddate>20090615</enddate><creator>Sharma, Madhulika</creator><creator>Brantley, Jennifer G.</creator><creator>Vassmer, Dianne</creator><creator>Chaturvedi, Gaurav</creator><creator>Baas, Jennifer</creator><creator>Vanden Heuvel, Gregory B.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20090615</creationdate><title>The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development</title><author>Sharma, Madhulika ; Brantley, Jennifer G. ; Vassmer, Dianne ; Chaturvedi, Gaurav ; Baas, Jennifer ; Vanden Heuvel, Gregory B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e1073-393029e600420cd7ce95240821b9c025205e76b1daa548ec73ed5cef8e600ad13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Animals, Newborn</topic><topic>Binding Sites</topic><topic>CCAAT-Enhancer-Binding Proteins - genetics</topic><topic>CCAAT-Enhancer-Binding Proteins - metabolism</topic><topic>Cell Line</topic><topic>Chromatin Immunoprecipitation</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - genetics</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Kidney - growth & development</topic><topic>Kidney - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sharma, Madhulika</creatorcontrib><creatorcontrib>Brantley, Jennifer G.</creatorcontrib><creatorcontrib>Vassmer, Dianne</creatorcontrib><creatorcontrib>Chaturvedi, Gaurav</creatorcontrib><creatorcontrib>Baas, Jennifer</creatorcontrib><creatorcontrib>Vanden Heuvel, Gregory B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Gene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sharma, Madhulika</au><au>Brantley, Jennifer G.</au><au>Vassmer, Dianne</au><au>Chaturvedi, Gaurav</au><au>Baas, Jennifer</au><au>Vanden Heuvel, Gregory B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development</atitle><jtitle>Gene</jtitle><addtitle>Gene</addtitle><date>2009-06-15</date><risdate>2009</risdate><volume>439</volume><issue>1</issue><spage>87</spage><epage>94</epage><pages>87-94</pages><issn>0378-1119</issn><eissn>1879-0038</eissn><abstract>The homeodomain protein Cux1 is highly expressed in the nephrogenic zone of the developing kidney where it functions to regulate cell proliferation. Here we show that Cux1 directly interacts with the co-repressor Grg4 (Groucho 4), a known effector of Notch signaling. Promoter reporter based luciferase assays revealed enhanced repression of
p27
kip1
promoter activity by Cux1 in the presence of Grg4. Chromatin immunoprecipitation (ChIP) assays demonstrated the direct interaction of Cux1 with
p27
kip1
in newborn kidney tissue
in vivo. ChIP assays also identified interactions of Cux1, Grg4, HDAC1, and HDAC3 with
p27
kip1
at two separate sites in the
p27
kip1
promoter. DNAse1 footprinting experiments revealed that Cux1 binds to the
p27
kip1
promoter on the sequence containing two Sp1 sites and a CCAAT box ∼
500 bp from the transcriptional start site, and to an AT rich sequence ∼
1.5 kb from the transcriptional start site. Taken together, these results identify Grg4 as an interacting partner for Cux1 and suggest a mechanism of
p27
kip1
repression by Cux1 during kidney development.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>19332113</pmid><doi>10.1016/j.gene.2009.03.014</doi><tpages>8</tpages></addata></record> |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Animals, Newborn Binding Sites CCAAT-Enhancer-Binding Proteins - genetics CCAAT-Enhancer-Binding Proteins - metabolism Cell Line Chromatin Immunoprecipitation Cyclin-Dependent Kinase Inhibitor p27 - genetics Cyclin-Dependent Kinase Inhibitor p27 - metabolism Gene Expression Regulation, Developmental Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Humans Kidney - growth & development Kidney - metabolism Mice Mice, Inbred C57BL Nuclear Proteins - genetics Nuclear Proteins - metabolism Promoter Regions, Genetic Protein Binding Repressor Proteins - genetics Repressor Proteins - metabolism |
| title | The homeodomain protein Cux1 interacts with Grg4 to repress p27 kip1 expression during kidney development |
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