Chong Jayhong A, Moran Magdalene M, Teichmann Martin, Kaczmarek J Stefan, Roeder Robert, Clapham David E
Department of Cardiology, Children's Hospital, Enders 1309, 320 Longwood Ave., Boston, MA 02115, USA.
Mol Cell Biol. 2005 Apr;25(7):2632-43. doi: 10.1128/MCB.25.7.2632-2643.2005.
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.
缺乏针对TATA结合蛋白（TBP）样因子（TLF）的直接靶点，这使得人们难以理解它们在基因表达中的作用。在此，我们报告人类TLF（也称为TBP相关因子2 [TRF2]）可激活许多不同的基因，包括1型神经纤维瘤病（NF1）基因。TLF的过表达会增加细胞中NF1 mRNA的量。在体内，TLF与NF1启动子的一个片段结合并上调其转录。在体外，纯化的TLF-TFIIA直接与细胞中TLF反应所需的相同NF1启动子片段结合。此外，小鼠中TLF的靶向缺失会降低NF1水平。相反，TLF通过隔离TFIIA来抑制由含TATA的c-fos启动子片段驱动的转录。TBP对NF1和c-fos启动子的影响与TLF相反，刺激c-fos启动子并抑制NF1转录。我们得出结论，TLF是一种转录功能调节因子，其靶点与TBP不同。
