Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2.
Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2.
复制标题
DLX2与淋巴增强子因子之间的功能相互作用调节MSX2。
DOI：
10.1093/nar/gkl689
复制
发表时间：
2006
影响因子：
14.9
通讯作者：
Amendt, Brad A.
中科院分区：
文献类型：
--
作者：
Diamond, Evan;Amen, Melanie;Hu, Qiaoyan;Espinoza, Herbert M.;Amendt, Brad A.
Dlx 2、类胚增强因子（Lef-1）和Msx 2转录因子是几种发育过程所必需的。为了了解这些因子对基因表达的控制，染色质免疫沉淀（ChIP）试验将Msx 2鉴定为Dlx 2和Lef-1的下游靶标。Dlx 2在几种细胞系中激活Msx 2启动子并结合DNA作为单体和二聚体。Lef-1 β-连环蛋白依赖性同种型最低限度地激活Msx 2启动子，而Lef-1 β-连环蛋白非依赖性同种型无活性，然而Dlx 2和两种Lef-1同种型的共表达协同激活Msx 2启动子。免疫共沉淀和蛋白下拉实验证明Lef-1与Dlx 2发生物理相互作用。Lef-1蛋白的缺失分析揭示了与Dlx 2协同作用所需的特定区域。Lef-1 β-连环蛋白结合结构域（βDB）对于其与Dlx 2的相互作用不是必需的。Msx 2可以自动调节其启动子并抑制Dlx 2活化。Msx 2对Dlx 2活化的抑制是剂量特异性的，并且两者都结合共同的DNA结合元件。这些转录机制与这些因子的时间和空间表达相关，并可能为控制几个发育过程提供机制。我们通过蛋白质相互作用和下游靶标的鉴定证明了Dlx 2，Msx 2和Lef-1的新转录活性。
Dlx2, Lymphoid Enhancer Factor (Lef-1) and Msx2 transcription factors are required for several developmental processes. To understand the control of gene expression by these factors, chromatin immunoprecipitation (ChIP) assays identified Msx2 as a downstream target of Dlx2 and Lef-1. Dlx2 activates the Msx2 promoter in several cell lines and binds DNA as a monomer and dimer. A Lef-1 β-catenin-dependent isoform minimally activates the Msx2 promoter and a Lef-1 β-catenin-independent isoform is inactive, however co-expression of Dlx2 and both Lef-1 isoforms synergistically activate the Msx2 promoter. Co-immunoprecipitation and protein pull-down experiments demonstrate Lef-1 physically interacts with Dlx2. Deletion analyses of the Lef-1 protein reveal specific regions required for synergism with Dlx2. The Lef-1 β-catenin binding domain (βDB) is not required for its interaction with Dlx2. Msx2 can auto-regulate its promoter and repress Dlx2 activation. Msx2 repression of Dlx2 activation is dose-specific and both bind a common DNA-binding element. These transcriptional mechanisms correlate with the temporal and spatial expression of these factors and may provide a mechanism for the control of several developmental processes. We demonstrate new transcriptional activities for Dlx2, Msx2 and Lef-1 through protein interactions and identification of downstream targets.
登录
查看更多内容
影响因子：
2.9
作者：
Bendall, AJ;Rincón-Limas, DE;Abate-Shen, C
通讯作者：
Abate-Shen, C
影响因子：
11.4
作者：
GIESE, K;GROSSCHEDL, R
通讯作者：
GROSSCHEDL, R
影响因子：
5.3
作者：
CATRON, KM;ILER, N;ABATE, C
通讯作者：
ABATE, C
影响因子：
14.9
作者：
Feledy, JA;Morasso, MI;Sargent, TD
通讯作者：
Sargent, TD
影响因子：
2.5
作者：
Bei, M;Stowell, S;Maas, R
通讯作者：
Maas, R