TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription:: Reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP
TATA-binding protein (TBP)-like factor (TLF) is a functional regulator of transcription:: Reciprocal regulation of the neurofibromatosis type 1 and c-fos genes by TLF/TRF2 and TBP
复制标题
DOI：
10.1128/mcb.25.7.2632-2643.2005
复制
发表时间：
2005-04-01
影响因子：
5.3
通讯作者：
Clapham, DE
中科院分区：
文献类型：
--
作者：
Chong, JA;Moran, MM;Clapham, DE
由于缺乏TATA结合蛋白（TBP）样因子（TLF）的直接靶点，使人们难以理解它们在基因表达中的作用。在这里，我们报告，人类TLF（也称为TBP相关因子2 [TRF 2]）激活了许多不同的基因，包括1型神经纤维瘤病（NF 1）基因。TLF的过表达增加了细胞中NF 1 mRNA的量。在体内，TLF结合并上调NF 1启动子片段的转录。在体外，纯化的TLF-TFIIA直接结合细胞中TLF应答所需的相同NF 1启动子片段。此外，小鼠中TLF的靶向缺失降低了NF 1水平。相反，TLF通过隔离TFIIA抑制由来自含TATA的c-fos启动子的片段驱动的转录。TBP以与TLF相反的方式影响NF 1和c-fos启动子，刺激c-fos启动子并抑制NF 1转录。我们的结论是，TLF是一个功能性的转录调节与TBP的目标不同。
The lack of direct targets for TATA-binding protein (TBP)-like factors (TLFs) confounds the understanding of their role in gene expression. Here we report that human TLF (also called TBP-related factor 2 [TRF2]) activates a number of different genes, including the neurofibromatosis type 1 (NF1) gene. The overexpression of TLF increases the amount of NF1 mRNA in cells. In vivo, TLF binds to and upregulates transcription from a fragment of the NF1 promoter. In vitro, purified TLF-TFIIA binds directly to the same NF1 promoter fragment that is required for TLF responsiveness in cells. Furthermore, targeted deletion of TLF in mice reduces NF1 levels. In contrast, TLF inhibits transcription driven by a fragment from the TATA-containing c-fos promoter by sequestering TFIIA. TBP affects the NF1 and c-fos promoters in a manner reciprocal to that of TLF, stimulating the c-fos promoter and inhibiting NF1 transcription. We conclude that TLF is a functional regulator of transcription with targets distinct from those of TBP.