Paredes Roberto, Arriagada Gloria, Cruzat Fernando, Olate Juan, Van Wijnen Andre, Lian Jane, Stein Gary, Stein Janet, Montecino Martin
Departamento de Biologia Molecular, Facultad de Ciencias Biologicas, Universidad de Concepcion, Casilla 160-C, Concepcion, Chile.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):269-71. doi: 10.1016/j.jsbmb.2004.03.076.
Bone-specific transcription of the osteocalcin (OC) gene is principally regulated by the Runx2 transcription factor and further stimulated in response to 1alpha,25-dihydroxy Vitamin D3 via its specific receptor (VDR). The rat OC gene promoter contains three recognition sites for Runx2 (sites A-C). Mutation of sites A and B, which flank the 1alpha,25-dihydroxy Vitamin D3-responsive element (VDRE), abolishes 1alpha,25-dihydroxy Vitamin D3-dependent enhancement of OC transcription, indicating a tight functional relationship between VDR and Runx2 factors. Additionally, the transcriptional co-activator p300 is recruited to the OC promoter by Runx2 where it up-regulates both basal and 1alpha,25-dihydroxy Vitamin D3-enhanced OC expression. Here, we present an overview of how in osteoblastic cells expressing OC, Runx2 modulates the 1alpha,25-dihydroxy Vitamin D3-dependent stimulation of the OC promoter by first recruiting transcriptional co-activators and then by further stabilizing the interaction of the VDR with the VDRE.
骨钙素（OC）基因的骨特异性转录主要受Runx2转录因子调控，并通过其特异性受体（VDR）对1α,25 - 二羟基维生素D3作出反应而进一步受到刺激。大鼠OC基因启动子包含三个Runx2识别位点（A - C位点）。位于1α,25 - 二羟基维生素D3反应元件（VDRE）两侧的A和B位点发生突变，会消除1α,25 - 二羟基维生素D3对OC转录的依赖性增强作用，这表明VDR和Runx2因子之间存在紧密的功能关系。此外，转录共激活因子p300被Runx2招募到OC启动子，在那里它上调基础和1α,25 - 二羟基维生素D3增强的OC表达。在此，我们概述了在表达OC的成骨细胞中，Runx2如何通过首先招募转录共激活因子，然后进一步稳定VDR与VDRE的相互作用，来调节1α,25 - 二羟基维生素D3对OC启动子的依赖性刺激。
