| 题名 | The essential role of MED27 in stabilizing the mediator complex for cardiac development and function |
| 作者 | |
| 通讯作者 | Fang，Xi |
| 发表日期 | 2024-11-01
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| DOI | |
| 发表期刊 | |
| ISSN | 0024-3205
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| EISSN | 1879-0631
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| 卷号 | 356 |
| 摘要 | Aim: Transcriptional regulation of gene expression plays a crucial role in orchestrating complex morphogenetic and molecular events during heart development and function. Mediator complex is an essential multi-subunit protein complex that governs gene expression in eukaryotic cells. Although Mediator subunits (MEDs) work integrally in the complex, individual MED component displays specialized functions. MED27, categorized as an Upper Tail subunit, possesses an as-yet-uncharacterized function. In this study, we aimed to investigate the physiological role of MED27 in cardiomyocytes. Materials and methods: we generated a Med27 floxed mouse line, which was further used to generate constitutive (cKO) and inducible (icKO) cardiomyocyte-specific Med27 knockout mouse models. Morphological, histological analysis and cardiac physiological studies were performed in Med27 cKO and icKO mutants. Transcriptional profiles were determined by RNA sequencing (RNAseq) analysis. Key fundings: Ablation of MED27 in developing mouse cardiomyocytes results in embryonic lethality, while its deletion in adult cardiomyocytes leads to heart failure and mortality. Similar to the ablation of another Upper Tail subunit, MED30 in cardiomyocytes, deletion of MED27 leads to decreased protein levels of most MEDs in cardiomyocytes. Interestingly, overexpression of MED30 fails to restore the protein levels of Mediator subunits in MED27-deficient cardiomyocytes, demonstrating that the role of MED27 in maintaining the integrity and stability of the Mediator complex is independent of MED30. Significance: Our results revealed an essential role of MED27 in cardiac development and function by maintaining the stability of the Mediator core. |
| 关键词 | |
| 相关链接 | [Scopus记录] |
| 语种 | 英语
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| 学校署名 | 其他
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| ESI学科分类 | BIOLOGY & BIOCHEMISTRY
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| Scopus记录号 | 2-s2.0-85202890457
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| 来源库 | Scopus
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| 引用统计 | |
| 成果类型 | 期刊论文 |
| 条目标识符 | http://sustech.caswiz.com/handle/2SGJ60CL/828585 |
| 专题 | 生命科学学院_系统生物学系 |
| 作者单位 | 1.Department of Cardiovascular Surgery,Peking University Shenzhen Hospital,School of Chemical Biology and Biotechnology,State Key Laboratory of Chemical Oncogenomics,Peking University Shenzhen Graduate School,Shenzhen,China 2.Department of Medicine,University of California San Diego,La Jolla,United States 3.Department of Cardiovascular Medicine,Translational Medicine Research Center,Zhujiang Hospital,Southern Medical University,Guangzhou,China 4.Department of Systems Biology,Southern University of Science and Technology,Shenzhen,China |
| 推荐引用方式 GB/T 7714 |
Zhu，Siting,Chen，Ze'e,Liu，Canzhao,et al. The essential role of MED27 in stabilizing the mediator complex for cardiac development and function[J]. Life Sciences,2024,356.
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| APA |
Zhu，Siting.,Chen，Ze'e.,Liu，Canzhao.,Duong，Janelle.,Tran，Tiana.,...&Ouyang，Kunfu.(2024).The essential role of MED27 in stabilizing the mediator complex for cardiac development and function.Life Sciences,356.
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| MLA |
Zhu，Siting,et al."The essential role of MED27 in stabilizing the mediator complex for cardiac development and function".Life Sciences 356(2024).
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| 条目包含的文件 | 条目无相关文件。 | |||||
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