Direct interaction of NRSF with TBP: chromatin reorganization and core promoter repression for neuron-specific gene transcription

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Abstract
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.