NRSF: A Coordinate Repressor of Neuron-Specific Genes Expressed in CNS Neural Progenitor Cells

Abstract

We have isolated cDNA clones encoding a novel zinc finger protein that silences neuron-specific gene expression, called the neuron-restrictive silencer factor (NRSF). NRSF binds a DNA sequence element called the neuron-restrictive silencer element (NRSE) that functions to repress neuronal genes in non-neuronal cells. Consensus NRSEs have been identified in at least 17 neuron-specific genes. Cloned NRSF can bind to multiple NRSEs and represses transcription in an NRSE-dependent manner. Expression of NRSF mRNA is detected in most non-neuronal tissues at several developmental stages. In the nervous system, NRSF mRNA is expressed in undifferentiated CNS neural progenitors but not in mature neurons. NRSF represents the first example of a vertebrate silencer protein that coordinately regulates a battery of cell type-specific genes. During development, NRSF may function as a master negative regulator of neuronal determination or differentiation in CNS stem cells.