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Previous Article | Next Article
The Journal of Neuroscience, February 15, 1998, 18(4):1280-1296
Neuronal Expression of Zinc Finger Transcription Factor REST/NRSF/XBR Gene
Kaia Palm1, Natale Belluardo2, Madis Metsis1, 3 and T õnis Timmusk1, 4 1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, S-171 77 Stockholm, Sweden, 2 Institute of Human Physiology, Faculty of Medicine, University of Catania, I-95125 Catania, Italy, 3 Gene Technology Center, Tallinn, EE0026 Estonia, and 4 Department of Developmental Neuroscience, Biomedical Center, Uppsala University, S-751 23 Uppsala, Sweden
The identification of a common cis-acting silencer element, a neuron-restrictive silencer element (NRSE), in multiple neuron-specific genes, together with the finding that zinc finger transcription factor REST/NRSF/XBR could confer NRSE-mediated silencing in non-neuronal cells, suggested that REST/NRSF/XBR is a master negative regulator of neurogenesis. Here we show that, although REST/NRSF/XBR expression decreases during neuronal development, it proceeds in the adult nervous system. In situ hybridization analysis revealed neuronal expression of rat REST/NRSF/XBR mRNA in adult brain, with the highest levels in the neurons of hippocampus, pons/medulla, and midbrain. The glutamate analog kainic acid increased REST/NRSF/XBR mRNA levels in various hippocampal and cortical neurons in vivo, suggesting that REST/NRSF/XBR has a role in neuronal activity-implied processes. Several alternatively spliced REST/NRSF/XBR mRNAs encoding proteins with nine, five, or four zinc finger motifs are transcribed from REST/NRSF/XBR gene. Two of these transcripts are generated by neuron-specific splicing of a 28-bp-long exon. Rat REST/NRSF/XBR protein isoforms differ in their DNA binding specificities; however, all mediate repression in transient expression assays. Our data suggest that REST/NRSF/XBR is a negative regulator rather than a transcriptional silencer of neuronal gene expression and counteracts with positive regulators to modulate target gene expression quantitatively in different cell types, including neurons.
Key words: REST; NRSF; XBR; transcription factor; zinc finger; silencer; negative regulator; repressor; gene structure; neuron-specific splicing; neuronal expression; brain; kainic acid; NRSE; BDNF
Copyright © 1998 Society for Neuroscience 0270-6474/98/1841280-17$05.00/0
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