Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis.

Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis.
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涉及同源域蛋白HOXA10和RUNX2的分子开关调节成骨细胞生成。

DOI:
10.1159/000151453
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发表时间:
2009
期刊:
Cells, tissues, organs
影响因子:
--
通讯作者:
Lian JB
Lian JB
中科院分区:
其他
文献类型:
--
作者:
Hassan MQ;Saini S;Gordon JA;van Wijnen AJ;Montecino M;Stein JL;Stein GS;Lian JB

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骨诱导BMP2信号通过诱导几类早期反应基因促进对成骨细胞表型的承诺。其中包括骨相关HOX因子、同源结构域(HD)、RUNX和OSTERIX蛋白。在这里,我们展示了BMP2诱导的转录因子之间的分子事件,这些转录因子构成了骨相关基因启动子上的分子开关网络,以协调它们在细胞分化过程中的时间表达。我们的研究提供了如下证据:(I)在成骨细胞成熟阶段,HOXA10、MSX2、DLX3和DLX5同源结构域转录因子选择性地结合在Runx2和骨钙素基因上;(Ii)这些因子与RUNX2参与骨特异基因染色质重塑,以抑制、激活和减弱转录。这些发现揭示了对成骨细胞相关基因表达的适当时机进行多水平控制的要求。
The osteoinductive BMP2 signal facilitates commitment to the osteoblast phenotype by inducing several classes of early response genes. Among these are bone related HOX factors, Homeodomain (HD), RUNX and OSTERIX proteins. Here we demonstrate molecular events among BMP2 induced transcription factors that constitute a network of molecular switches on promoters of bone related genes to coordinate their temporal expression during cellular differentiation. Our studies provide evidence for (i) selective association of HOXA10, MSX2, DLX3 and DLX5 homeodomain transcription factors on Runx2 and Osteocalcin genes at stages of osteoblast maturation; and (ii) participation of these factors with RUNX2 in chromatin remodeling of bone specific genes for repression, activation, and attenuation of transcription. These findings reveal the requirement for multiple levels of control for the appropriate timing of osteoblast related gene expression.
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