The Neuron-Restrictive Silencer Factor (NRSF): A Coordinate Repressor of Multiple Neuron-Specific Genes

Abstract

The neuron-restrictive silencer factor (NRSF) binds a DNA sequence element, called the neuron-restrictive silencer element (NRSE), that represses neuronal gene transcription in nonneuronal cells. Consensus NRSEs have been identified in 18 neuron-specific genes. Complementary DNA clones encoding a functional fragment of NRSF were isolated and found to encode a novel protein containing eight noncanonical zinc fingers. Expression of NRSF mRNA was detected in most nonneuronal tissues at several developmental stages. In the nervous system, NRSF mRNA was detected in undifferentiated neuronal progenitors, but not in differentiated neurons. NRSF represents the first example of a vertebrate silencer protein that potentially regulates a large battery of cell type-specific genes, and therefore may function as a master negative regulator of neurogenesis.

Regulation of the NRSF/REST gene by methylation and CREB affects the cellular phenotype of small-cell lung cancer

“…NRSF/REST, a member of the kru¨ppel-type zinc-finger family, binds to the neuron-restrictive silencer element (NRSE/repressor element 1) and acts as a negative regulator of neuronal gene transcription. As NRSEs were identified for the rat SCG10 and other neuronal genes, NRSF was initially regarded as a master negative regulator of neurogenesis (Schoenherr and Anderson, 1995). Indeed, the number of putative NRSF/REST-regulated genes has dramatically risen since (Bruce et al, 2004).…”

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

“…REST is located on chromosome 4q12, consists of 4 exons, and encodes a 1,097-amino acid protein 15,16 (Figures 2B and 2C). REST is a zinc finger protein that regulates gene expression throughout the body.…”

“…16,17 It has a critical function as a transcriptional repressor during embryonic development and neurogenesis so it is also called neuron-restrictive silencer element. 15 Additionally, REST has different roles in several cellular mechanisms, such as oncogenic and tumor-suppressor functions, hematopoietic, cardiac and osteoblast differentiation, and effects on chromatin-modifying enzymes. [17][18][19][20][21] The pathophysiologic mechanisms underlying HGF remain enigmatic; however, excessive accumulation of extracellular matrix components, particularly collagen type I, seem to contribute to the clinical-pathologic manifestations.…”

A transgenic mouse Class‐III β tubulin reporter using yellow fluorescent protein

“…The present results also provide insight into the regulation of β-tubulin III by the zinc-finger transcription factor NRSF (neuron-restrictive silencing factor), whose function, in part, is to repress the expression of neuron-specific genes in non-neuronal cells (Chong et al , 1995;Lunyak and Rosenfeld, 2005;Schoenherr and Anderson, 1995). NRSF binds to a conserved 21 bp element called an NRSE (neuron-restrictive silencer element), and exerts its influence by recruiting enzymes that alter chromatin structure (Lunyak and Rosenfeld, 2005).…”

“…The mouse β-tubulin III NRSE is located in the first intron (Schoenherr et al, 1996). Anderson and colleagues (Chen et al, 1998;Schoenherr and Anderson, 1995;Schoenherr et al, 1996) have shown that the β-tubulin III gene is regulated in part by the NRSF. It is interesting to note that in this work, the β-tubulin III -YFP construct introduced into the mouse did not include the NRSE, The neuronal accumulation, as well as the lack of non-neuronal accumulation of YFP, provides strong evidence that the control of β-tubulin III expression is not solely dependent on NRSF (Dennis et al, 2002).…”