Format

Send to

Choose Destination
Oncotarget. 2016 Jun 21;7(25):37471-37486. doi: 10.18632/oncotarget.9650.

Osterix acetylation at K307 and K312 enhances its transcriptional activity and is required for osteoblast differentiation.

Author information

1
Department of Developmental Genetics, Nanjing Medical University, Nanjing, P.R. China.
2
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
3
Molecular Endocrinology Laboratory, Department of Endocrinology, Odense University Hospital, Odense C, Denmark.

Abstract

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.

KEYWORDS:

CBP; Pathology Section; acetylation; osteoblast differentiation; osterix

PMID:
27250035
PMCID:
PMC5122325
DOI:
10.18632/oncotarget.9650
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Impact Journals, LLC Icon for PubMed Central
Loading ...
Support Center