Synergistic activation of cardiac genes by myocardin and Tbx5.
Myocardial differentiation is associated with the activation and expression of an array of cardiac specific genes. However, the transcriptional networks that control cardiac gene expression are not completely understood. Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coa...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3163680?pdf=render |
| _version_ | 1818036691272728576 |
|---|---|
| author | Chunbo Wang Dongsun Cao Qing Wang Da-Zhi Wang |
| author_facet | Chunbo Wang Dongsun Cao Qing Wang Da-Zhi Wang |
| author_sort | Chunbo Wang |
| collection | DOAJ |
| description | Myocardial differentiation is associated with the activation and expression of an array of cardiac specific genes. However, the transcriptional networks that control cardiac gene expression are not completely understood. Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of Serum Response Factor (SRF) and is able to potently activate cardiac and smooth muscle gene expression during development. We hypothesize that myocardin discriminates between cardiac and smooth muscle specific genes by associating with distinct co-factors. Here, we show that myocardin directly interacts with Tbx5, a member of the T-box family of transcription factors involved in the Holt-Oram syndrome. Tbx5 synergizes with myocardin to activate expression of the cardiac specific genes atrial natriuretic factor (ANF) and alpha myosin heavy chain (α-MHC), but not that of smooth muscle specific genes SM22 or smooth muscle myosin heavy chain (SM-MHC). We found that this synergistic activation of shared target genes is dependent on the binding sites for Tbx5, T-box factor-Binding Elements (TBEs). Myocardin and Tbx5 physically interact and their interaction domains were mapped to the basic domain and the coil domain of myocardin and Tbx5, respectively. Our analysis demonstrates that the Tbx5G80R mutation, which leads to the Holt-Oram syndrome in humans, failed to synergize with myocardin to activate cardiac gene expression. These data uncover a key role for Tbx5 and myocardin in establishing the transcriptional foundation for cardiac gene activation and suggest that the interaction of myocardin and Tbx5 maybe involved in cardiac development and diseases. |
| first_indexed | 2024-12-10T07:14:58Z |
| format | Article |
| id | doaj.art-c6c5af4d34604b5a892cf91de38b5feb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T07:14:58Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c6c5af4d34604b5a892cf91de38b5feb2022-12-22T01:57:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2424210.1371/journal.pone.0024242Synergistic activation of cardiac genes by myocardin and Tbx5.Chunbo WangDongsun CaoQing WangDa-Zhi WangMyocardial differentiation is associated with the activation and expression of an array of cardiac specific genes. However, the transcriptional networks that control cardiac gene expression are not completely understood. Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of Serum Response Factor (SRF) and is able to potently activate cardiac and smooth muscle gene expression during development. We hypothesize that myocardin discriminates between cardiac and smooth muscle specific genes by associating with distinct co-factors. Here, we show that myocardin directly interacts with Tbx5, a member of the T-box family of transcription factors involved in the Holt-Oram syndrome. Tbx5 synergizes with myocardin to activate expression of the cardiac specific genes atrial natriuretic factor (ANF) and alpha myosin heavy chain (α-MHC), but not that of smooth muscle specific genes SM22 or smooth muscle myosin heavy chain (SM-MHC). We found that this synergistic activation of shared target genes is dependent on the binding sites for Tbx5, T-box factor-Binding Elements (TBEs). Myocardin and Tbx5 physically interact and their interaction domains were mapped to the basic domain and the coil domain of myocardin and Tbx5, respectively. Our analysis demonstrates that the Tbx5G80R mutation, which leads to the Holt-Oram syndrome in humans, failed to synergize with myocardin to activate cardiac gene expression. These data uncover a key role for Tbx5 and myocardin in establishing the transcriptional foundation for cardiac gene activation and suggest that the interaction of myocardin and Tbx5 maybe involved in cardiac development and diseases.http://europepmc.org/articles/PMC3163680?pdf=render |
| spellingShingle | Chunbo Wang Dongsun Cao Qing Wang Da-Zhi Wang Synergistic activation of cardiac genes by myocardin and Tbx5. PLoS ONE |
| title | Synergistic activation of cardiac genes by myocardin and Tbx5. |
| title_full | Synergistic activation of cardiac genes by myocardin and Tbx5. |
| title_fullStr | Synergistic activation of cardiac genes by myocardin and Tbx5. |
| title_full_unstemmed | Synergistic activation of cardiac genes by myocardin and Tbx5. |
| title_short | Synergistic activation of cardiac genes by myocardin and Tbx5. |
| title_sort | synergistic activation of cardiac genes by myocardin and tbx5 |
| url | http://europepmc.org/articles/PMC3163680?pdf=render |
| work_keys_str_mv | AT chunbowang synergisticactivationofcardiacgenesbymyocardinandtbx5 AT dongsuncao synergisticactivationofcardiacgenesbymyocardinandtbx5 AT qingwang synergisticactivationofcardiacgenesbymyocardinandtbx5 AT dazhiwang synergisticactivationofcardiacgenesbymyocardinandtbx5 |