TRIM28 Regulates Dlk1 Expression in Adipogenesis
The tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockd...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7245 |
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| author | Hsin-Pin Lu Chieh-Ju Lin Wen-Ching Chen Yao-Jen Chang Sheng-Wei Lin Hsin-Hui Wang Ching-Jin Chang |
| author_facet | Hsin-Pin Lu Chieh-Ju Lin Wen-Ching Chen Yao-Jen Chang Sheng-Wei Lin Hsin-Hui Wang Ching-Jin Chang |
| author_sort | Hsin-Pin Lu |
| collection | DOAJ |
| description | The tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockdown of Trim28 by transducing lentivirus-carrying shRNAs impairs the differentiation of 3T3-L1 preadipocytes, demonstrated by morphological observation and gene expression analysis. To understand the molecular mechanism of Trim28-mediated adipogenesis, the RNA-seq was performed to find out the possible Trim28-regulated genes. Dlk1 (delta-like homolog 1) was increased in Trim28 knockdown 3T3-L1 cells both untreated and induced to differentiation. <i>Dlk1</i> is an imprinted gene and known as an inhibitor of adipogenesis. Further knockdown of Dlk1 in Trim28 knockdown 3T3-L1 would rescue cell differentiation. The epigenetic analysis showed that DNA methylation of Dlk1 promoter and differentially methylated regions (DMRs) was not altered significantly in Trim28 knockdown cells. However, compared to control cells, the histone methylation on the <i>Dlk1</i> promoter was increased at H3K4 and decreased at H3K27 in Trim28 knockdown cells. Finally, we found Trim28 might be recruited by transcription factor E2f1 to regulate <i>Dlk1</i> expression. The results imply Trim28-Dlk1 axis is critical for adipogenesis. |
| first_indexed | 2024-03-10T15:55:10Z |
| format | Article |
| id | doaj.art-a3b10b555c04418082934922a460466b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:55:10Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a3b10b555c04418082934922a460466b2023-11-20T15:43:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119724510.3390/ijms21197245TRIM28 Regulates Dlk1 Expression in AdipogenesisHsin-Pin Lu0Chieh-Ju Lin1Wen-Ching Chen2Yao-Jen Chang3Sheng-Wei Lin4Hsin-Hui Wang5Ching-Jin Chang6Graduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, TaiwanGraduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, TaiwanGraduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 11529, TaiwanInstitute of Biological Chemistry, Academia Sinica, Taipei 11529, TaiwanDepartment of Pediatrics, Division of Pediatric Immunology and Nephrology, Taipei Veterans General Hospital, Taipei 11217, TaiwanGraduate Institute of Biochemical Sciences, College of Life Science, National Taiwan University, Taipei 10617, TaiwanThe tripartite motif-containing protein 28 (TRIM28) is a transcription corepressor, interacting with histone deacetylase and methyltransferase complexes. TRIM28 is a crucial regulator in development and differentiation. We would like to investigate its function and regulation in adipogenesis. Knockdown of Trim28 by transducing lentivirus-carrying shRNAs impairs the differentiation of 3T3-L1 preadipocytes, demonstrated by morphological observation and gene expression analysis. To understand the molecular mechanism of Trim28-mediated adipogenesis, the RNA-seq was performed to find out the possible Trim28-regulated genes. Dlk1 (delta-like homolog 1) was increased in Trim28 knockdown 3T3-L1 cells both untreated and induced to differentiation. <i>Dlk1</i> is an imprinted gene and known as an inhibitor of adipogenesis. Further knockdown of Dlk1 in Trim28 knockdown 3T3-L1 would rescue cell differentiation. The epigenetic analysis showed that DNA methylation of Dlk1 promoter and differentially methylated regions (DMRs) was not altered significantly in Trim28 knockdown cells. However, compared to control cells, the histone methylation on the <i>Dlk1</i> promoter was increased at H3K4 and decreased at H3K27 in Trim28 knockdown cells. Finally, we found Trim28 might be recruited by transcription factor E2f1 to regulate <i>Dlk1</i> expression. The results imply Trim28-Dlk1 axis is critical for adipogenesis.https://www.mdpi.com/1422-0067/21/19/7245TRIM28Dlk1adipogenesisDNA methylationhistone modification |
| spellingShingle | Hsin-Pin Lu Chieh-Ju Lin Wen-Ching Chen Yao-Jen Chang Sheng-Wei Lin Hsin-Hui Wang Ching-Jin Chang TRIM28 Regulates Dlk1 Expression in Adipogenesis International Journal of Molecular Sciences TRIM28 Dlk1 adipogenesis DNA methylation histone modification |
| title | TRIM28 Regulates Dlk1 Expression in Adipogenesis |
| title_full | TRIM28 Regulates Dlk1 Expression in Adipogenesis |
| title_fullStr | TRIM28 Regulates Dlk1 Expression in Adipogenesis |
| title_full_unstemmed | TRIM28 Regulates Dlk1 Expression in Adipogenesis |
| title_short | TRIM28 Regulates Dlk1 Expression in Adipogenesis |
| title_sort | trim28 regulates dlk1 expression in adipogenesis |
| topic | TRIM28 Dlk1 adipogenesis DNA methylation histone modification |
| url | https://www.mdpi.com/1422-0067/21/19/7245 |
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