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

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.
Mesh Terms:
Binding Sites, Cell Line, Chromatin, Conserved Sequence, Gene Silencing, Humans, Neurons, Promoter Regions, Genetic, Protein Structure, Tertiary, Repressor Proteins, TATA-Box Binding Protein, Transcription Factors, Transcription, Genetic
Nucleic Acids Res.
Date: Jun. 16, 2004
Download Curated Data For This Publication
113650
Switch View:
  • Interactions 6