Analysis of HDAC1-mediated regulation of Runx2-induced osteopontin gene expression in C3h10t1/2 cells

作者:Zhang, Zhongli; Deepak, Vishwa; Meng, Lingyi; Wang, Linghui; Li, Yushan; Jiang, Qing; Zeng, Xianlu; Liu, Wenguang*
来源:Biotechnology Letters, 2012, 34(2): 197-203.
DOI:10.1007/s10529-011-0756-8

摘要

Histone deacetylases (HDACs) deacetylate lysine residues of histone and non-histone proteins and thereby regulate the cell-cycle, gene expression, and several other processes. We have analyzed the effects of HDAC1 on Runx2-mediated regulation of osteopontin (OPN) promoter activation and gene expression in mesenchymal progenitor C3h10t1/2 cells and show that co-expression of HDAC1 along with Runx2 results in down-regulation of Runx2-induced OPN mRNA expression during both the proliferation and differentiation stages of C3h10t1/2 cells. Luciferase assay results revealed that HDAC1 efficiently down-regulated Runx2-stimulated OPN promoter activity in a dose-dependent manner whereas TSA relieved the HDAC1-mediated repression and up-regulated the Runx2-induced OPN promoter activity and mRNA expression. In vivo HDAC1 co-localized and physically interacted with Runx2 and associated with the OPN promoter. Thus, HDAC1 not only plays a critical role in regulation of Runx2-stimulated expression of osteogenic genes, like OPN, but also regulate the proliferation and differentiation stages of mesenchymal progenitor cells, such as C3h10t1/2.

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