A coregulatory network of NR2F1 and microRNA-140.
Both nuclear receptor subfamily 2 group F member 1 (NR2F1) and microRNAs (miRNAs) have been shown to play critical roles in the developing and functional inner ear. Based on previous studies suggesting interplay between NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to b...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3857795?pdf=render |
| _version_ | 1818264503735812096 |
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| author | David Y Chiang David W Cuthbertson Fernanda R Ruiz Na Li Fred A Pereira |
| author_facet | David Y Chiang David W Cuthbertson Fernanda R Ruiz Na Li Fred A Pereira |
| author_sort | David Y Chiang |
| collection | DOAJ |
| description | Both nuclear receptor subfamily 2 group F member 1 (NR2F1) and microRNAs (miRNAs) have been shown to play critical roles in the developing and functional inner ear. Based on previous studies suggesting interplay between NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to better understand the regulatory mechanisms of inner ear development and functional maturation.Using a bioinformatic approach, we identified 11 potential miRNAs that might coregulate target genes with NR2F1 and analyzed their targets and potential roles in physiology and disease. We selected 6 miRNAs to analyze using quantitative real-time (qRT) -PCR and found that miR-140 is significantly down-regulated by 4.5-fold (P=0.004) in the inner ear of NR2F1 knockout (Nr2f1(-/-)) mice compared to wild-type littermates but is unchanged in the brain. Based on this, we performed chromatin-immunoprecipitation followed by qRT-PCR and confirmed that NR2F1 directly binds and regulates both miR-140 and Klf9 in vivo. Furthermore, we performed luciferase reporter assay and showed that miR-140 mimic directly regulates KLF9-3'UTR, thereby establishing and validating an example coregulatory network involving NR2F1, miR-140, and Klf9.We have described and experimentally validated a novel tissue-dependent coregulatory network for NR2F1, miR-140, and Klf9 in the inner ear and we propose the existence of many such coregulatory networks important for both inner ear development and function. |
| first_indexed | 2024-12-12T19:35:57Z |
| format | Article |
| id | doaj.art-0eac57accfa340af902f3704cf953ab2 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T19:35:57Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0eac57accfa340af902f3704cf953ab22022-12-22T00:14:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8335810.1371/journal.pone.0083358A coregulatory network of NR2F1 and microRNA-140.David Y ChiangDavid W CuthbertsonFernanda R RuizNa LiFred A PereiraBoth nuclear receptor subfamily 2 group F member 1 (NR2F1) and microRNAs (miRNAs) have been shown to play critical roles in the developing and functional inner ear. Based on previous studies suggesting interplay between NR2F1 and miRNAs, we investigated the coregulation between NR2F1 and miRNAs to better understand the regulatory mechanisms of inner ear development and functional maturation.Using a bioinformatic approach, we identified 11 potential miRNAs that might coregulate target genes with NR2F1 and analyzed their targets and potential roles in physiology and disease. We selected 6 miRNAs to analyze using quantitative real-time (qRT) -PCR and found that miR-140 is significantly down-regulated by 4.5-fold (P=0.004) in the inner ear of NR2F1 knockout (Nr2f1(-/-)) mice compared to wild-type littermates but is unchanged in the brain. Based on this, we performed chromatin-immunoprecipitation followed by qRT-PCR and confirmed that NR2F1 directly binds and regulates both miR-140 and Klf9 in vivo. Furthermore, we performed luciferase reporter assay and showed that miR-140 mimic directly regulates KLF9-3'UTR, thereby establishing and validating an example coregulatory network involving NR2F1, miR-140, and Klf9.We have described and experimentally validated a novel tissue-dependent coregulatory network for NR2F1, miR-140, and Klf9 in the inner ear and we propose the existence of many such coregulatory networks important for both inner ear development and function.http://europepmc.org/articles/PMC3857795?pdf=render |
| spellingShingle | David Y Chiang David W Cuthbertson Fernanda R Ruiz Na Li Fred A Pereira A coregulatory network of NR2F1 and microRNA-140. PLoS ONE |
| title | A coregulatory network of NR2F1 and microRNA-140. |
| title_full | A coregulatory network of NR2F1 and microRNA-140. |
| title_fullStr | A coregulatory network of NR2F1 and microRNA-140. |
| title_full_unstemmed | A coregulatory network of NR2F1 and microRNA-140. |
| title_short | A coregulatory network of NR2F1 and microRNA-140. |
| title_sort | coregulatory network of nr2f1 and microrna 140 |
| url | http://europepmc.org/articles/PMC3857795?pdf=render |
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