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Essential role of TEA domain transcription factors in the negative regulation of the MYH7 gene by thyroid hormone and its receptors
http://hdl.handle.net/10271/00003570
http://hdl.handle.net/10271/0000357015c30dfe-ae50-44ac-b78d-6bb06fa56236
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (832.0 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2019-07-10 | |||||
| タイトル | ||||||
| タイトル | Essential role of TEA domain transcription factors in the negative regulation of the MYH7 gene by thyroid hormone and its receptors | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| その他のタイトル | ||||||
| その他のタイトル | 甲状腺ホルモンとその受容体によるMYH7遺伝子への負の調節においてTEAドメイン転写因子が果たす必須な機能 | |||||
| 言語 | ja | |||||
| 著者 |
岩鬼, 裕之
× 岩鬼, 裕之 |
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| 書誌情報 |
en : PLOS ONE 巻 9, 号 4, p. e88610, 発行日 2014-04-29 |
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| 出版者 | ||||||
| 出版者 | PLOS (Public Library of Science) | |||||
| 言語 | en | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | MYH7 (also referred to as cardiac myosin heavy chain β) gene expression is known to be repressed by thyroid hormone (T3). However, the molecular mechanism by which T3 inhibits the transcription of its target genes (negative regulation) remains to be clarified, whereas those of transcriptional activation by T3 (positive regulation) have been elucidated in detail. Two MCAT (muscle C, A, and T) sites and an A/T-rich region in the MYH7 gene have been shown to play a critical role in the expression of this gene and are known to be recognized by the TEAD/TEF family of transcription factors (TEADs). Using a reconstitution system with CV-1 cells, which has been utilized in the analysis of positive as well as negative regulation, we demonstrate that both T3 receptor (TR) β1 and α1 inhibit TEAD-dependent activation of the MYH7 promoter in a T3 dose-dependent manner. TRβ1 bound with GC-1, a TRβ-selective T3 analog, also repressed TEAD-induced activity. Although T3-dependent inhibition required the DNA-binding domain (DBD) of TRβ1, it remained after the putative negative T3-responsive elements were mutated. A co-immunoprecipitation study demonstrated the in vivo association of TRβ1 with TEAD-1, and the interaction surfaces were mapped to the DBD of the TRβ1 and TEA domains of TEAD-1, both of which are highly conserved among TRs and TEADs, respectively. The importance of TEADs in MYH7 expression was also validated with RNA interference using rat embryonic cardiomyocyte H9c2 cells. These results indicate that T3-bound TRs interfere with transactivation by TEADs via protein-protein interactions, resulting in the negative regulation of MYH7 promoter activity. | |||||
| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位の区分 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | doctoral | |||||
| 言語 | en | |||||
| 学位の分野 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 医学系研究科 | |||||
| 言語 | ja | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 13802 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 浜松医科大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-01-18 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 乙第557号 | |||||
| EISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1932-6203 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 24781449 | |||||
| 出版社DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1371/journal.pone.0088610 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
