Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation.
Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation.
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Osterix 在 K307 和 K312 处乙酰化可增强其转录活性，并且是成骨细胞分化所必需的
DOI：
10.18632/oncotarget.9650
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发表时间：
2016-06-21
期刊：
影响因子：
--
通讯作者：
Ma C
中科院分区：
文献类型：
--
作者：
Lu J;Qu S;Yao B;Xu Y;Jin Y;Shi K;Shui Y;Pan S;Chen L;Ma C
Osterix（Osx）是成骨细胞分化和骨形成的重要转录因子。Osx表达调控的精确分子机制尚未完全了解。在本研究中，我们发现在细胞中，用组蛋白脱乙酰酶抑制剂曲古抑菌素A和异羟肟酸处理后，内源性和外源性Osx蛋白均增加。同时，免疫沉淀的结果表明，Osx是一个乙酰化的蛋白质和CREB结合蛋白（CBP），和效率较低的p300，乙酰化Osx。免疫共沉淀法和免疫荧光法分别证明了CBP和Osx的相互作用和共定位。另外，K307和K312被鉴定为Osx的乙酰化位点。相比之下，HDAC 4，组蛋白脱乙酰酶（HDAC），观察到相互作用和共定位与Osx。HDAC 4被证明介导Osx的脱乙酰化。此外，我们发现Osx的乙酰化增强了其稳定性、DNA结合能力和转录活性。最后，我们证明了Osx的乙酰化是C2C12细胞成骨分化所必需的。总之，我们的研究结果提供了证据表明，CBP介导的乙酰化和HDAC4介导的去乙酰化在Osx的修饰中具有关键作用，因此在成骨细胞分化中很重要。
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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