Oct-1 counteracts autoinhibition of Runx2 DNA binding to form a novel runx2/Oct-1 complex on the promoter of the mammary gland-specific gene β-casein
Oct-1 counteracts autoinhibition of Runx2 DNA binding to form a novel runx2/Oct-1 complex on the promoter of the mammary gland-specific gene β-casein
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DOI：
10.1128/mcb.25.8.3182-3193.2005
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发表时间：
2005-04-01
影响因子：
5.3
通讯作者：
Shore, P
中科院分区：
文献类型：
--
作者：
Inman, CK;Li, N;Shore, P
转录因子Runx 2对于许多骨特异性基因的表达至关重要，并且主要被认为是骨发育的主要调节因子。Runx 2也在乳腺上皮细胞中表达，但其在乳腺中的作用尚未确定。在这里，我们表明，Runx 2形成一个新的复合物与无处不在的转录因子Oct-1调节乳腺特异性基因β-酪蛋白的表达。Runx 2/Oct-1复合物在酪蛋白启动子中高度保守的Runx/八聚体元件上形成。染色质免疫沉淀，RNA干扰，启动子诱变和瞬时表达分析被用来证明Runx 2/Oct-1复合物有助于β-酪蛋白基因的转录调控。复合物的分析揭示了Runx 2的N-末端和C-末端区域中DNA结合的自抑制结构域。Oct-1通过与Runx 2的C-末端区域相互作用刺激Runx 2募集到β-酪蛋白启动子，表明Oct-1通过缓解Runx 2 DNA结合的自抑制来刺激Runx 2募集。这些发现表明Runx 2与Oct-1合作，并有助于乳腺特异性基因的表达。
The transcription factor Runx2 is essential for the expression of a number of bone-specific genes and is primarily considered a master regulator of bone development. Runx2 is also expressed in mammary epithelial cells, but its role in the mammary gland has not been established. Here we show that Runx2 forms a novel complex with the ubiquitous transcription factor Oct-1 to regulate the expression of the mammary gland-specific gene beta-casein. The Runx2/Oct-1 complex forms on a Runx/octamer element which is highly conserved in casein promoters. Chromatin immunoprecipitation, RNA interference, promoter mutagenesis, and transient expression analyses were used to demonstrate that the Runx2/Oct-1 complex contributes to the transcriptional regulation of the beta-casein gene. Analysis of the complex revealed autoinhibitory domains for DNA binding in both the N-terminal and the C-terminal regions of Runx2. Oct-1 stimulates the recruitment of Runx2 to the beta-casein promoter by interacting with the C-terminal region of Runx2, suggesting that Oct-1 stimulates Runx2 recruitment by relieving the autoinhibition of Runx2 DNA binding. These findings demonstrate that Runx2 collaborates with Oct-1 and contributes to the expression of a mammary gland-specific gene.