Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells
Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regula...
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| Veröffentlicht in: | Nucleic acids research 2016-01, Vol.44 (1), p.387-401 |
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| creator | Akhade, Vijay Suresh Dighe, Shrinivas Nivrutti Kataruka, Shubhangini Rao, Manchanahalli R Satyanarayana |
| description | Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes. |
| doi_str_mv | 10.1093/nar/gkv1023 |
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LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes.</description><identifier>ISSN: 0305-1048</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkv1023</identifier><identifier>PMID: 26446991</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Alcohol Oxidoreductases - metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism ; beta Catenin - metabolism ; Binding Sites ; Biomarkers ; Cell Differentiation - genetics ; Cell Line ; Co-Repressor Proteins - metabolism ; DNA-Binding Proteins - metabolism ; Down-Regulation ; Gene Expression ; Gene Expression Regulation ; Genes, Reporter ; Histones - metabolism ; Humans ; Male ; Mice ; Promoter Regions, Genetic ; Protein Binding ; RNA ; RNA, Long Noncoding - genetics ; Spermatogonia - cytology ; Spermatogonia - metabolism ; Transcription Factor 4 ; Transcription, Genetic ; Wnt Signaling Pathway</subject><ispartof>Nucleic acids research, 2016-01, Vol.44 (1), p.387-401</ispartof><rights>The Author(s) 2015. 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Published by Oxford University Press on behalf of Nucleic Acids Research. 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-3ac437a3dccdc783a1fe241cd56e4605b3509b14c9113a2f7324823222483b883</citedby><cites>FETCH-LOGICAL-c377t-3ac437a3dccdc783a1fe241cd56e4605b3509b14c9113a2f7324823222483b883</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/PMC4705645/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705645/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26446991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Akhade, Vijay Suresh</creatorcontrib><creatorcontrib>Dighe, Shrinivas Nivrutti</creatorcontrib><creatorcontrib>Kataruka, Shubhangini</creatorcontrib><creatorcontrib>Rao, Manchanahalli R Satyanarayana</creatorcontrib><title>Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. We have identified Ctbp1 as the co-repressor and its occupancy on mrhl RNA promoter depends on both β-catenin and TCF4. Upon Wnt signaling activation, Ctbp1 mediated histone repression marks increase at the mrhl RNA promoter. We also demonstrate that Wnt signaling induced mrhl RNA down regulation results in an up regulation of various meiotic differentiation marker genes.</description><subject>Alcohol Oxidoreductases - metabolism</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism</subject><subject>beta Catenin - metabolism</subject><subject>Binding Sites</subject><subject>Biomarkers</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line</subject><subject>Co-Repressor Proteins - metabolism</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation</subject><subject>Genes, Reporter</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Spermatogonia - cytology</subject><subject>Spermatogonia - metabolism</subject><subject>Transcription Factor 4</subject><subject>Transcription, Genetic</subject><subject>Wnt Signaling Pathway</subject><issn>0305-1048</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1LHTEUhkOx1KvtqnvJslBGc3IyH9kURKwKWkFaugy5mczc2Exym8wo_nvn4lV05-osznNezstDyFdgh8AkHgWdjvp_d8A4fiALwIoXQlZ8hywYsrIAJppdspfzLWMgoBSfyC6vhKikhAXxV9asdHB5oLGjf8NIs-uD9i701IV2MralbbwPNNl-8np0MWzAIa089XGGQgyFie2Gv_l1PN_QIU7Z0ry2adBj7GNw2lNjvc-fycdO-2y_bOc--fPz9PfJeXF5fXZxcnxZGKzrsUBtBNYaW2NaUzeoobNcgGnLyoqKlUssmVyCMBIANe9q5KLhyPk8cNk0uE9-POWup-VgW2PDmLRX6-QGnR5U1E693QS3Un28U6JmZSXKOeDbNiDF_5PNoxpc3lTQwc7tFNSSyRLrhr0DrZhkAA3O6Pcn1KSYc7Ldy0fA1EalmlWqrcqZPnhd4oV9doePQsGcAg</recordid><startdate>20160108</startdate><enddate>20160108</enddate><creator>Akhade, Vijay Suresh</creator><creator>Dighe, Shrinivas Nivrutti</creator><creator>Kataruka, Shubhangini</creator><creator>Rao, Manchanahalli R Satyanarayana</creator><general>Oxford University Press</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>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20160108</creationdate><title>Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells</title><author>Akhade, Vijay Suresh ; Dighe, Shrinivas Nivrutti ; Kataruka, Shubhangini ; Rao, Manchanahalli R Satyanarayana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-3ac437a3dccdc783a1fe241cd56e4605b3509b14c9113a2f7324823222483b883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Alcohol Oxidoreductases - metabolism</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism</topic><topic>beta Catenin - metabolism</topic><topic>Binding Sites</topic><topic>Biomarkers</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line</topic><topic>Co-Repressor Proteins - metabolism</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation</topic><topic>Genes, Reporter</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>Spermatogonia - cytology</topic><topic>Spermatogonia - metabolism</topic><topic>Transcription Factor 4</topic><topic>Transcription, Genetic</topic><topic>Wnt Signaling Pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Akhade, Vijay Suresh</creatorcontrib><creatorcontrib>Dighe, Shrinivas Nivrutti</creatorcontrib><creatorcontrib>Kataruka, Shubhangini</creatorcontrib><creatorcontrib>Rao, Manchanahalli R Satyanarayana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akhade, Vijay Suresh</au><au>Dighe, Shrinivas Nivrutti</au><au>Kataruka, Shubhangini</au><au>Rao, Manchanahalli R Satyanarayana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2016-01-08</date><risdate>2016</risdate><volume>44</volume><issue>1</issue><spage>387</spage><epage>401</epage><pages>387-401</pages><issn>0305-1048</issn><eissn>1362-4962</eissn><abstract>Long non coding RNAs (lncRNAs) have emerged as important regulators of various biological processes. LncRNAs also behave as response elements or targets of signaling pathway(s) mediating cellular function. Wnt signaling is important in regulating mammalian spermatogenesis. Mrhl RNA negatively regulates canonical Wnt pathway and gets down regulated upon Wnt signaling activation in mouse spermatogonial cells. Also, mrhl RNA regulates expression of genes pertaining to Wnt pathway and spermatogenesis by binding to chromatin. In the present study, we delineate the detailed molecular mechanism of Wnt signaling induced mrhl RNA down regulation in mouse spermatogonial cells. Mrhl RNA has an independent transcription unit and our various experiments like Chromatin Immunoprecipitation (in cell line as well as mouse testis) and shRNA mediated down regulation convincingly show that β-catenin and TCF4, which are the key effector proteins of the Wnt signaling pathway are required for down regulation of mrhl RNA. 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| subjects | Alcohol Oxidoreductases - metabolism Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism beta Catenin - metabolism Binding Sites Biomarkers Cell Differentiation - genetics Cell Line Co-Repressor Proteins - metabolism DNA-Binding Proteins - metabolism Down-Regulation Gene Expression Gene Expression Regulation Genes, Reporter Histones - metabolism Humans Male Mice Promoter Regions, Genetic Protein Binding RNA RNA, Long Noncoding - genetics Spermatogonia - cytology Spermatogonia - metabolism Transcription Factor 4 Transcription, Genetic Wnt Signaling Pathway |
| title | Mechanism of Wnt signaling induced down regulation of mrhl long non-coding RNA in mouse spermatogonial cells |
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