Neuronal Gene Regulation by the Neural — Restrictive Silencer (NRS)
Neural restrictive silencer (NRS) is a 22-bp-long cell type-specific transcriptional silencer element that is found in a variety of neural-specific genes.1,2 NRS represses transcription in non-neuronal cells, thereby allowing gene expression only in neurons. The sequence-specific DNA-binding protein that recognizes NRS (NRSF, also named REST) is expressed essentially in undifferentiated neuronal precursors and non-neuronal cells and functions as a transcriptional repressor.3 NRSF represents the first example of a vertebrate silencer factor that regulates a large battery of neuronal phenotype-specific genes, and therefore may function as a general negative regulator of neuronal terminal differentiation. However, in contrast to what was originally thought, recent evidence suggests that NRS is found in many genes involved in the cholinergic, GABAergic, and glutamatergic neuronal transmission, but may not be evident in the genes that relate to monoaminergic neurotransmission. Here I would like to discuss the possibility that NRS represses neurons to acquire monoaminergic function and that the role of NRS could be somehow limited in monoaminergic or catecholaminergic systems.
KeywordsTyrosine Hydroxylase Neuronal Differentiation Atrial Natriuretic Peptide Phenyl Ethanolamine Catecholaminergic System
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- 6.N. Mori, Neural-restrictive silencer (NRS) and its regulatory factor NRSF/REST, Exp. Med. (in Japanese) 15, 446–454(1997)Google Scholar
- 12.J. J. Schimmel, L. Crew, S. Roffler-Tarlov, and D. M. Chikaraichi, 4.5 kb of the rat tyrosine hydroxylase 5’ flanking sequence directs tissue specific expression during development and contains consensus sites for multiple transcription factors, Mol. Brain Res. 74, 1–14 (1999).CrossRefGoogle Scholar