Cargando…
Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation
Osterix (Osx) is an essential transcription factor involved in osteoblast differentiation and bone formation. The precise molecular mechanisms of the regulation of Osx expression are not fully understood. In the present study, we found that in cells, both endogenous and exogenous Osx protein increas...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122325/ https://www.ncbi.nlm.nih.gov/pubmed/27250035 http://dx.doi.org/10.18632/oncotarget.9650 |
_version_ | 1782469556753661952 |
---|---|
author | Lu, Jianlei Qu, Shuang Yao, Bing Xu, Yuexin Jin, Yucui Shi, Kaikai Shui, Yifang Pan, Shiyang Chen, Li Ma, Changyan |
author_facet | Lu, Jianlei Qu, Shuang Yao, Bing Xu, Yuexin Jin, Yucui Shi, Kaikai Shui, Yifang Pan, Shiyang Chen, Li Ma, Changyan |
author_sort | Lu, Jianlei |
collection | PubMed |
description | Osterix (Osx) is an essential transcription factor involved in osteoblast differentiation and bone formation. The precise molecular mechanisms of the regulation of Osx expression are not fully understood. In the present study, we found that in cells, both endogenous and exogenous Osx protein increased after treatment with histone deacetylase inhibitors Trichostatin A and hydroxamic acid. Meanwhile, the results of immunoprecipitation indicated that Osx was an acetylated protein and that the CREB binding protein (CBP), and less efficiently p300, acetylated Osx. The interaction and colocalization of CBP and Osx were demonstrated by Co-immunoprecipitation and immunofluorescence, respectively. In addition, K307 and K312 were identified as the acetylated sites of Osx. By contrast, HDAC4, a histone deacetylase (HDAC), was observed to interact and co-localize with Osx. HDAC4 was demonstrated to mediate the deacetylation of Osx. Moreover, we found that acetylation of Osx enhanced its stability, DNA binding ability and transcriptional activity. Finally, we demonstrated that acetylation of Osx was required for the osteogenic differentiation of C2C12 cells. Taken together, our results provide evidence that CBP-mediated acetylation and HDAC4-mediated deacetylation have critical roles in the modification of Osx, and thus are important in osteoblast differentiation. |
format | Online Article Text |
id | pubmed-5122325 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51223252016-12-05 Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation Lu, Jianlei Qu, Shuang Yao, Bing Xu, Yuexin Jin, Yucui Shi, Kaikai Shui, Yifang Pan, Shiyang Chen, Li Ma, Changyan Oncotarget Research Paper: Pathology Osterix (Osx) is an essential transcription factor involved in osteoblast differentiation and bone formation. The precise molecular mechanisms of the regulation of Osx expression are not fully understood. In the present study, we found that in cells, both endogenous and exogenous Osx protein increased after treatment with histone deacetylase inhibitors Trichostatin A and hydroxamic acid. Meanwhile, the results of immunoprecipitation indicated that Osx was an acetylated protein and that the CREB binding protein (CBP), and less efficiently p300, acetylated Osx. The interaction and colocalization of CBP and Osx were demonstrated by Co-immunoprecipitation and immunofluorescence, respectively. In addition, K307 and K312 were identified as the acetylated sites of Osx. By contrast, HDAC4, a histone deacetylase (HDAC), was observed to interact and co-localize with Osx. HDAC4 was demonstrated to mediate the deacetylation of Osx. Moreover, we found that acetylation of Osx enhanced its stability, DNA binding ability and transcriptional activity. Finally, we demonstrated that acetylation of Osx was required for the osteogenic differentiation of C2C12 cells. Taken together, our results provide evidence that CBP-mediated acetylation and HDAC4-mediated deacetylation have critical roles in the modification of Osx, and thus are important in osteoblast differentiation. Impact Journals LLC 2016-05-26 /pmc/articles/PMC5122325/ /pubmed/27250035 http://dx.doi.org/10.18632/oncotarget.9650 Text en Copyright: © 2016 Lu et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper: Pathology Lu, Jianlei Qu, Shuang Yao, Bing Xu, Yuexin Jin, Yucui Shi, Kaikai Shui, Yifang Pan, Shiyang Chen, Li Ma, Changyan Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title | Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title_full | Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title_fullStr | Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title_full_unstemmed | Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title_short | Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation |
title_sort | osterix acetylation at k307 and k312 enhances its transcriptional activity and is required for osteoblast differentiation |
topic | Research Paper: Pathology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122325/ https://www.ncbi.nlm.nih.gov/pubmed/27250035 http://dx.doi.org/10.18632/oncotarget.9650 |
work_keys_str_mv | AT lujianlei osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT qushuang osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT yaobing osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT xuyuexin osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT jinyucui osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT shikaikai osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT shuiyifang osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT panshiyang osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT chenli osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation AT machangyan osterixacetylationatk307andk312enhancesitstranscriptionalactivityandisrequiredforosteoblastdifferentiation |