title: Direct interaction of NRSF with TBP: chromatin reorganization and core promoter repression for neuron-specific gene transcription.
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.
authors.affiliation: Department of Molecular Genetics, National Institute for Longevity Sciences, Gengo 36-3, Morioka, Oobu, Aichi 474-8522, Japan.
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Murai
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Naruse
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shaul
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Agata
authors.forename: Nozomu
authors.initials: N
authors.lastname: Mori
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002843:Chromatin / Q000648:ultrastructure; D017124:Conserved Sequence; D020868:Gene Silencing; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D000099229:RE1-Silencing Transcription Factor
chemical_list: D002843:Chromatin; D012097:Repressor Proteins; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D000099229:RE1-Silencing Transcription Factor