Direct interaction of NRSF with TBP: chromatin reorganization and core promoter repression for neuron-specific gene transcription
Direct interaction of NRSF with TBP: chromatin reorganization and core promoter repression for neuron-specific gene transcription
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DOI：
10.1093/nar/gkh550
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发表时间：
2004-06-01
影响因子：
14.9
通讯作者：
Mori, N
中科院分区：
文献类型：
--
作者：
Murai, K;Naruse, Y;Mori, N
神经限制性沉默因子NRSF（也称为REST）结合神经元细胞类型选择性沉默元件，介导非神经元细胞和神经元祖细胞中神经元特异性基因的转录抑制。两个抑制域（RD-1和RD-2）分别出现在其n端和c端区域。RD-1招募mSin3和HDAC，从而通过诱导染色质结构重组来抑制转录。然而，对于这种全局抑制如何成为特定启动子的抑制，以及NRSF-HDAC复合体是否可以与每个特定启动子的转录核心因子相互作用，我们知之甚少。在这里我们展示了NRSF与核心启动因子相互作用的证据，包括tata结合蛋白（TBP）。NRSF-TBP相互作用发生在N端和c端大部分NRSF的线性片段和TBP的c端部分之间。NRSF的RD-2突变体失去了tbp结合活性，并且无法抑制外源引入的TGTA启动子的转录。这些结果表明NRSF c -末端结构域与TBP之间的直接相互作用对于NRSF c -末端抑制机制至关重要。因此，NRSF的RD-1和RD-2抑制域利用染色质依赖性和染色质非依赖性机制，它们可能在神经发育和调节的不同阶段分离。
Neural restrictive silencer factor, NRSF (also known as REST) binds a neuronal cell type selective silencer element to mediate transcriptional repression of neuron-specific genes in non-neuronal cells and neuronal progenitors. Two repression domains (RD-1 and RD-2) occur in its N-terminal and C-terminal regions, respectively. RD-1 recruits mSin3 and HDAC, thereby inhibiting transcription by inducing reorganization of the chromatin structure. However, little is known about how such global repression becomes promoter-specific repression or whether the NRSF-HDAC complex can interact with transcriptional core factors at each specific promoter. Here we show evidence that NRSF interacts with core promoter factors, including TATA-binding protein (TBP). The NRSF-TBP interaction occurred between the linear segments of the N- and C-terminal-most portions of NRSF and the C-terminal half of TBP. A RD-2 mutant of NRSF lost the TBP-binding activity and was unable to repress transcription at an exogenously introduced TGTA promoter. These results indicate that the direct interaction between the NRSF C-terminal domain and TBP is essential for the C-terminal repression mechanism of NRSF. Thus, the RD-1 and RD-2 repression domains of NRSF utilize both chromatin-dependent and chromatin-independent mechanisms, which may be segregated at various stages of neural development and modulation.