Brain-derived neurotrophic factor expression in vivo is under the control of neuron-restrictive silencer element

Neuron-restrictive silencer element (NRSE) has been identified in multiple neuron-specific genes. This element has been shown to mediate repression of neuronal gene transcription in nonneuronal cells. A palindromic NRSE (NRSE BDNF) is present in the proximal, region of brain-derived neurotrophic fact or (BDNF) promoter II. Using in vitro binding assays, we establish that the upper half-site is largely responsible for the NRSEBDNF activity. To delin eate the in vivo role of NRSE in the regulation of rat BDNF gene, promoter constructs with intact and mutated NRSEBDNF were introduced into transgenic mice. Our data show that NRSEBDNF is controlling the activity of BDNF prom oters I and II in the brain, thymus, and lung, i.e. in the tissues in which the intact reporter gene and endogenous BDNF mRNAs are expressed. Mutation of NRSEBDNF did not lead to the ectopic activation of the reporter gene in any other nonneural tissues. In the brain, NRSEBDNF is involved in the rep ression of basal and kainic acid-induced expression from BDNF promoters I a nd II in neurons. However, NRSEBDNF does not control the activity of the BD NF gene in nonneuronal cells of brain.