NEURONAL EXPRESSION OF ZINC-FINGER TRANSCRIPTION FACTOR REST NRSF/XRBGENE/

The identification of a common cis-acting silencer element, a neuron-r estrictive 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, s uggested that REST/NRSF/XBR is a master negative regulator of neurogen esis. Here we show that, although REST/NRSF/XBR expression decreases d uring neuronal development, ii proceeds in the adult nervous system, I n 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 kaini c 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 RES T/NRSF/XBR mRNAs encoding proteins with nine, five, or four zinc finge r motifs are transcribed from REST/NRSF/XBR gene. Two of these transcr ipts are generated by neuron-specific splicing of a 28-bp-long exon. R at REST/NRSF/XBR protein isoforms differ in their DNA binding specific ities; however, all mediate repression in transient expression assays. Our data suggest that REST/NRSF/XBR is a negative regulator rather th an a transcriptional silencer of neuronal gene expression and countera cts with positive regulators to modulate target gene expression quanti tative in different cell types, including neurons.