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The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes
1Division of Biology 216-76, California Institute of Technology, Pasadena 91125.
Summary
The neuron-restrictive silencer factor (NRSF) silences neuronal genes in nonneuronal cells. This novel silencer protein may act as a master regulator of neurogenesis by controlling cell type-specific gene expression.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The neuron-restrictive silencer factor (NRSF) binds neuron-restrictive silencer elements (NRSEs).
- NRSEs repress neuronal gene transcription in nonneuronal cells.
- 18 neuron-specific genes contain consensus NRSEs.
Purpose of the Study:
- To isolate and characterize the NRSF protein.
- To investigate the expression pattern of NRSF.
- To determine the role of NRSF in neurogenesis.
Main Methods:
- Isolation of complementary DNA clones encoding a functional NRSF fragment.
- Protein analysis to identify structural features (e.g., zinc fingers).
- Messenger RNA (mRNA) expression analysis in various tissues and developmental stages.
Main Results:
- A novel protein with eight noncanonical zinc fingers was identified as NRSF.
- NRSF mRNA was detected in most nonneuronal tissues.
- In the nervous system, NRSF mRNA was found in neuronal progenitors but absent in differentiated neurons.
Conclusions:
- NRSF is the first identified vertebrate silencer protein.
- NRSF potentially regulates a large set of cell type-specific genes.
- NRSF may function as a master negative regulator of neurogenesis.