Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials.
Cell-context dependent TCF/LEF expression and function: alternative tales of repression, de-repression and activation potentials.
复制标题
DOI：
10.1615/critreveukargeneexpr.v21.i3.10
复制
发表时间：
2011
影响因子：
1.6
通讯作者：
Byers SW
中科院分区：
文献类型：
--
作者：
Mao CD;Byers SW
Wnt信号通过汇聚在一个小的DNA结合因子家族，即T细胞因子/淋巴增强因子（TCF/LEF）家族上来控制发育和成体组织稳态期间的细胞特化和命运。响应于Wnt信号，TCF/LEF成员经历从抑制到激活的转录转换，这部分地由核β-连环蛋白结合和辅激活因子复合物的募集介导。在哺乳动物中，这种转录开关的特异性和微调也通过四个成员（TCF 7，TCF 7 L1，TCF 7 L2和LEF 1）和许多变体的细胞环境依赖性表达来实现，这些变体显示出不同的DNA结合亲和力和特异性，抑制强度，激活潜力和调节剂。TCF 7/LEF 1变异体由选择性启动子、选择性外显子盒和选择性供体/受体剪接位点产生，允许组合插入/排除模块化功能和调控结构域。在这篇综述中，我们提出了越来越多的证据TCF 7/LEF 1变体的表达和功能与细胞谱系和细胞状态的相互依赖性。我们还说明了如何p53和核受体家族的转录因子，已知控制细胞的命运和抑制Wnt信号，可能参与微调TCF 7/LEF 1抑制/激活潜力。
Wnt signaling controls cell specification and fate during development and adult tissue homeostasis by converging on a small family of DNA binding factors, the T-cell factor/lymphoid enhancer factor (TCF/LEF) family. In response to Wnt signals, TCF/LEF members undergo a transcriptional switch from repression to activation mediated in part by nuclear β-catenin binding and recruitment of co-activator complexes. In mammals, the specificity and fine tuning of this transcriptional switch is also achieved by the cell-context-dependent expression of four members (TCF7, TCF7L1, TCF7L2, and LEF1) and numerous variants, which display differential DNA binding affinity and specificity, repression strength, activation potential, and regulators. TCF7/LEF1 variants are generated by alternative promoters, alternative exon cassettes, and alternative donor/acceptor splicing sites, allowing combinatorial insertion/exclusion of modular functional and regulatory domains. In this review we present mounting evidence for the interdependency of TCF7/LEF1 variant expression and functions with cell lineage and cell state. We also illustrate how the p53 and nuclear receptor family of transcription factors, known to control cell fate and to inhibit Wnt signaling, may participate in the fine tuning of TCF7/LEF1 repression/activation potentials.
登录
查看更多内容
影响因子：
5.3
作者：
Alpatov, R;Munguba, GC;Sugrue, SP
通讯作者：
Sugrue, SP
影响因子：
3.7
作者：
Beildeck ME;Gelmann EP;Byers SW
通讯作者：
Byers SW
影响因子：
3.7
作者：
Beildeck ME;Islam M;Shah S;Welsh J;Byers SW
通讯作者：
Byers SW
影响因子：
5.3
作者：
Alpatov, Roman;Shi, Yujiang;Sugrue, Stephen P.
通讯作者：
Sugrue, Stephen P.
影响因子：
5.3
作者：
Atcha, Fawzia A.;Syed, Adeela;Waterman, Marian L.
通讯作者：
Waterman, Marian L.