Published online 14 June 2004
Nucleic Acids Research, 2004, Vol. 32, No. 10 3180-3189
© 2004 Oxford University Press
Direct interaction of NRSF with TBP: chromatin reorganization and core promoter repression for neuron-specific gene transcription
1 Department of Molecular Genetics, National Institute for Longevity Sciences, Gengo 36-3, Morioka, Oobu, Aichi 474-8522, Japan, 2 Horizontal Medical Research Organization (HMRO), Faculty of Medicine, Kyoto University, Yoshidakonoe, Sakyo, Kyoto 606-8501, Japan, 3 Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel, 4 Department of Aging Intervention, National Institute for Longevity Sciences (NILS), Gengo 36-3, Morioka, Oobu, Aichi 474-8522, Japan and 5 Department of Molecular Anatomy and Neurobiology, Nagasaki University School of Medicine, Sakamoto 1-12-4, Nagasaki 852-8523, Japan
*To whom correspondence should be addressed at: Department of Molecular Anatomy and Neurobiology, Nagasaki University School of Medicine, Sakamoto 1-12-4, Nagasaki 852-8523, Japan. Tel: +81 95 849 7017; Fax: +81 95 849 7036; Email: morinosm{at}net.nagasaki-u.ac.jp
Present address:
Yoshihisa Naruse, Department of Anatomy, Kyoto Prefecture University of Medicine, Japan
Received March 28, 2004; Accepted March 29, 2004
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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Ovcharenko and M. A. Nobrega Identifying synonymous regulatory elements in vertebrate genomes Nucleic Acids Res., July 1, 2005; 33(suppl_2): W403 - W407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Plaisance, G. Niederhauser, F. Azzouz, V. Lenain, J.-A. Haefliger, G. Waeber, and A. Abderrahmani The Repressor Element Silencing Transcription Factor (REST)-mediated Transcriptional Repression Requires the Inhibition of Sp1 J. Biol. Chem., January 7, 2005; 280(1): 401 - 407. [Abstract] [Full Text] [PDF]
|
|