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

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 nonneuronal 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