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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...

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Autores principales: Lu, Jianlei, Qu, Shuang, Yao, Bing, Xu, Yuexin, Jin, Yucui, Shi, Kaikai, Shui, Yifang, Pan, Shiyang, Chen, Li, Ma, Changyan
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
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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.
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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
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