THE NEURON-RESTRICTIVE SILENCER ELEMENT - A DUAL ENHANCER SILENCER CRUCIAL FOR PATTERNED EXPRESSION OF A NICOTINIC RECEPTOR GENE IN THE BRAIN/

The neuron-restrictive silencer element (NRSE) has been identified in several neuronal genes and confers neuron specificity by silencing tra nscription in nonneuronal cells, NRSE is present in the promoter of th e neuronal nicotinic acetylcholine receptor beta 2-subunit gene that d etermines its neuron-specific expression in the nervous system, Using transgenic mice, we show that NRSE may either silence or enhance trans cription depending on the cellular context within the nervous system, In vitro in neuronal cells, NRSE activates transcription of synthetic promoters when located downstream in the 5' untranslated region, or at less than 50 bp upstream from the TATA box, but switches to a silence r when located further upstream. In contrast, in nonneuronal cells NRS E always functions as a silencer. Antisense RNA inhibition shows that the NRSE-binding protein REST contributes to the activation of transcr iption in neuronal cells.