SIRT1 deacetylates the cardiac transcription factor Nkx2.5 and inhibits its transcriptional activity
| Autor: | Zhu Qin Zhang, Xiaoqiang Tang, Lei Han, Shu Ting Liang, De-Pei Liu, Xiao-Feng Chen, Gong-Hong Wei, Hou-Zao Chen, Wei Zheng, Yun Biao Lu, Han Ma |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Biology Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine stomatognathic system Sirtuin 1 Transcription (biology) Animals Humans Myocytes Cardiac Transcription factor Homeodomain Proteins Multidisciplinary Myocardium HEK 293 cells Acetylation respiratory system Rats 030104 developmental biology HEK293 Cells Biochemistry embryonic structures biology.protein cardiovascular system Homeobox Protein Nkx-2.5 Homeobox Protein deacetylase NAD+ kinase 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep36576 |
| Popis: | The homeodomain transcription factor Nkx2.5/Csx is critically essential for heart specification, morphogenesis, and homeostasis. Acetylation/deacetylation is important for the localization, stability and activation of transcription factors. It remains unknown how Nkx2.5 is deacetylated and how Nkx2.5 acetylation determines its activity. In this study, we provide evidence that the NAD+-dependent class III protein deacetylase SIRT1 deacetylates Nkx2.5 in cardiomyocytes and represses the transcriptional activity of Nkx2.5. We show that SIRT1 interacts with the C-terminus of Nkx2.5 and deacetylates Nkx2.5 at lysine 182 in the homeodomain. The mutation of Nkx2.5 at lysine 182 reduces its transcriptional activity. Furthermore, SIRT1 inhibits the transcriptional activity of Nkx2.5 and represses the expression of its target genes partly by reducing Nkx2.5 binding to its co-factors, including SRF and TBX5. Taken together, these findings demonstrate that SIRT1 deacetylates Nkx2.5 and inhibits the transcriptional activity of Nkx2.5. |
| Databáze: | OpenAIRE |
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